Nahum Sonenberg

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs (2008)

Rong, Liwei, Livingstone, Mark, Sukarieh, Rami, Petroulakis, Emmanuel, Gingras, Anne-Claude, Crosby, Katherine, ...

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the...

Weak binding affinity of human 4EHP for mRNA cap analogs (2007)

Zuberek, Joanna, Kubacka, Dorota, Jablonowska, Agnieszka, Jemielity, Jacek, Stepinski, Janusz, Sonenberg, Nahum, ...

Ribosome recruitment to the majority of eukaryotic mRNAs is facilitated by the interaction of the cap binding protein, eIF4E, with the mRNA 5′ cap structure. eIF4E stimulates translation through...

Stimulation of picornavirus replication by the poly(A) tail in a cell-free extract is largely independent of the poly(A) binding protein (PABP) (2007)

Svitkin, Yuri V., Costa-Mattioli, Mauro, Herdy, Barbara, Perreault, Sandra, Sonenberg, Nahum

Picornavirus infectivity is dependent on the RNA poly(A) tail, which binds the poly(A) binding protein (PABP). PABP was reported to stimulate viral translation and RNA synthesis. Here, we studied...

Weak binding affinity of human 4EHP for mRNA cap analogs (2007)

Zuberek, Joanna, Kubacka, Dorota, Jablonowska, Agnieszka, Jemielity, Jacek, Stepinski, Janusz, Sonenberg, Nahum, ...

Ribosome recruitment to the majority of eukaryotic mRNAs is facilitated by the interaction of the cap binding protein, eIF4E, with the mRNA 5′ cap structure. eIF4E stimulates translation through...

Regulation of poly(A) binding protein function in translation: Characterization of the Paip2 homolog, Paip2B (2006)

Berlanga, Juan José, Baass, Alexis, Sonenberg, Nahum

The 5′ cap and 3′ poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding...

Regulation of Poly(A) binding protein function in translation: Characterization of the Paip2 homolog, Paip2B (2006)

Berlanga, Juan José, Baass, Alexis, Sonenberg, Nahum

The 5′ cap and 3′ poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding...

RNA aptamers to mammalian initiation factor 4G inhibit cap-dependent translation by blocking the formation of initiation factor complexes (2006)

Miyakawa, Shin, Oguro, Akihiro, Ohtsu, Takashi, Imataka, Hiroaki, Sonenberg, Nahum, Nakamura, Yoshikazu

Eukaryotic translation initiation factor 4G (eIF4G) plays a crucial multimodulatory role in mRNA translation and decay by interacting with other translation factors and mRNA-associated proteins. In...

RNA aptamers to mammalian initiation factor 4G inhibit cap-dependent translation by blocking the formation of initiation factor complexes (2006)

Miyakawa, Shin, Oguro, Akihiro, Ohtsu, Takashi, Imataka, Hiroaki, Sonenberg, Nahum, Nakamura, Yoshikazu

Eukaryotic translation initiation factor 4G (eIF4G) plays a crucial multimodulatory role in mRNA translation and decay by interacting with other translation factors and mRNA-associated proteins. In...

Regulation of Poly(A) binding protein function in translation: Characterization of the Paip2 homolog, Paip2B (2006)

Berlanga, Juan José, Baass, Alexis, Sonenberg, Nahum

The 5′ cap and 3′ poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding...

RNA aptamers to mammalian initiation factor 4G inhibit cap-dependent translation by blocking the formation of initiation factor complexes (2006)

Miyakawa, Shin, Oguro, Akihiro, Ohtsu, Takashi, Imataka, Hiroaki, Sonenberg, Nahum, Nakamura, Yoshikazu

Eukaryotic translation initiation factor 4G (eIF4G) plays a crucial multimodulatory role in mRNA translation and decay by interacting with other translation factors and mRNA-associated proteins. In...

Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation. (2005)

Bordeleau, Marie-Eve, Matthews, James, Wojnar, Joanna M., Lindqvist, Lisa, Novac, Olivia, Jankowsky, Eckhard, ...

RNA helicases are the largest group of enzymes in eukaryotic RNA metabolism. The DEXD/H-box putative RNA helicases form the helicase superfamily II, whose members are defined by seven highly...

Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP (2005)

Tettweiler, Gritta, Miron, Mathieu, Jenkins, Mark, Sonenberg, Nahum, Lasko, Paul F.

eIF4E, the mRNA 5′ cap-binding protein, is regulated by its binding protein (4E-BP), a downstream target of phosphatidylinositol-3-OH kinase [PI(3)K] signaling. We show that Drosophila 4E-BP...

Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP (2005)

Tettweiler, Gritta, Miron, Mathieu, Jenkins, Mark, Sonenberg, Nahum, Lasko, Paul F.

eIF4E, the mRNA 5′ cap-binding protein, is regulated by its binding protein (4E-BP), a downstream target of phosphatidylinositol-3-OH kinase [PI(3)K] signaling. We show that Drosophila 4E-BP...

High affinity RNA for mammalian initiation factor 4E interferes with mRNA-cap binding and inhibits translation (2005)

MOCHIZUKI, KIYOTAKA, OGURO, AKIHIRO, OHTSU, TAKASHI, SONENBERG, NAHUM, NAKAMURA, YOSHIKAZU

The eukaryotic translation initiation factor 4F (eIF4F) consists of three polypeptides (eIF4A, eIF4G, and eIF4E) and is responsible for recruiting ribosomes to mRNA. eIF4E recognizes the mRNA...

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms (2005)

Kahvejian, Avak, Svitkin, Yuri V., Sukarieh, Rami, M'Boutchou, Marie-Noël, Sonenberg, Nahum

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′...

Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP (2005)

Tettweiler, Gritta, Miron, Mathieu, Jenkins, Mark, Sonenberg, Nahum, Lasko, Paul F.

eIF4E, the mRNA 5′ cap-binding protein, is regulated by its binding protein (4E-BP), a downstream target of phosphatidylinositol-3-OH kinase [PI(3)K] signaling. We show that Drosophila 4E-BP...

Upstream and downstream of mTOR (2004)

Hay, Nissim, Sonenberg, Nahum

The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in...

UNR, a new partner of poly(A)-binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant (2004)

Chang, Tsung-Cheng, Yamashita, Akio, Chen, Chyi-Ying A., Yamashita, Yukiko, Zhu, Wenmiao, Durdan, Simon, ...

Messenger RNA decay mediated by the c-fos major protein coding-region determinant of instability (mCRD) is a useful system for studying translationally coupled mRNA turnover. Among the five...

The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. (2003)

Yang, Hsin-Sheng, Jansen, Aaron P., Komar, Anton A., Zheng, Xiaojing, Merrick, William C., Costes, Sylvain, ...

Pdcd4 is a novel transformation suppressor that inhibits tumor promoter-induced neoplastic transformation and the activation of AP-1-dependent transcription required for transformation. A yeast...

RNA aptamers to initiation factor 4A helicase hinder cap-dependent translation by blocking ATP hydrolysis (2003)

OGURO, AKIHIRO, OHTSU, TAKASHI, SVITKIN, YURI V., SONENBERG, NAHUM, NAKAMURA, YOSHIKAZU

The mammalian translation initiation factor 4A (eIF4A) is a prototype member of the DEAD-box RNA helicase family that couples ATPase activity to RNA binding and unwinding. In the crystal form, eIF4A...

Phosphorylation of eIF4E attenuates its interaction with mRNA 5' cap analogs by electrostatic repulsion: Intein-mediated protein ligation strategy to obtain phosphorylated protein (2003)

ZUBEREK, JOANNA, WYSLOUCH-CIESZYNSKA, ALEKSANDRA, NIEDZWIECKA, ANNA, DADLEZ, MICHAL, STEPINSKI, JANUSZ, AUGUSTYNIAK, WOJCIECH, ...

Phosphorylation of the eukaryotic initiation factor eIF4E in response to mitogenic stimuli and cytokines is implicated in the regulation of the initiation step of translation. It still remains...

A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus (2002)

Tang, Shao Jun, Reis, Gerald, Kang, Hyejin, Gingras, Anne-Claude, Sonenberg, Nahum, Schuman, Erin M.

Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTIP) that endures for more than an hour requires both...

Eukaryotic translation initiation factor 4AIII (eIF4AIII) is functionally distinct from eIF4AI and eIF4AII. (1999)

Li, Qiyu, Imataka, Hiroaki, Morino, Shigenobu, Rogers, George W., Richter-Cook, Nancy J., Merrick, William C., ...

Eukaryotic initiation factor 4A (eIF4A) is an RNA-dependent ATPase and ATP-dependent RNA helicase that is thought to melt the 5' proximal secondary structure of eukaryotic mRNAs to facilitate...

Conserved tertiary structural elements in the 5' nontranslated region of cardiovirus, aphthovirus and hepatitis A virus RNAs (1993)

Le, Shu-Yun, Chen, Jih-H., Sonenberg, Nahum, Maizel, Jacob V.

Statistical analyses of RNA folding In 5′ nontranslated regions (5’NTR) of encephalomyocarditis virus, Theller's murlne encephalomyelltls virus, foot-and-mouth disease virus, and hepatitis A...

Identification of nuclear cap specific proteins in HeLa cells (1987)

Rozen, Florence, Sonenberg, Nahum

Two polypeptides of apparent molecular mass of 20 and 115 kilodaltons in nuclear fractions from HeLa cells were shown to recognize and be crosslinked to the cap structure of eukaryotic mRNAs in a...

ATP/Mg++-dependent cross-linking of cap binding proteins to the 5' end of eukaryotic mRNA (1981)

Sonenberg, Nahum

Two proteins of apparent molecular weights of 28,000 and 50,000 daltons were shown to recognize and cross-link specifically to the 5′ cap end of oxidized reovirus mRNA. Cross-linking of these...

Interaction of a limited set of proteins with different mRNAs and protection of 5'-caps against pyrophosphatase digestion in initiation complexes (1979)

Sonenberg, Nahum, Morgan, Maureen A., Testa, Douglas, Colonno, Richard J., Shatkin, Aaron J.

A variety of 5′- 3H-methyl-labeled, oxidized viral mRNAs were used as probes for detecting in wheat germ initiation complexes proteins that interact with, and can be cross-linked to, the 5′-cap...

Analysis of terminal structures of RNA from potato virus X (1978)

Sonenberg, Nahum, Shatkin, Aaron J., Ricciardi, Robert P., Rubin, Michal, Goodman, Robert M.

The 5′-end structure of potato virus X RNA was determined following enzymatic methylation in vitro A single 3H group was introduced into the 2′-position of the 5′-penultimate residue and the...

A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding

Karim, Muhammad M., Svitkin, Yuri V., Kahvejian, Avak, De Crescenzo, Gregory, Costa-Mattioli, Mauro, Sonenberg, Nahum

The eukaryotic mRNA 3′ poly(A) tail and the 5′ cap cooperate to synergistically enhance translation. This interaction is mediated by the cap-binding protein eIF4E, the poly(A) binding protein...

Proteolysis of human eukaryotic translation initiation factor eIF4GII, but not eIF4GI, coincides with the shutoff of host protein synthesis after poliovirus infection

Gradi, Alessandra, Svitkin, Yuri V., Imataka, Hiroaki, Sonenberg, Nahum

Eukaryotic initiation factor (eIF) 4GI is a component of the cap-binding protein complex eIF4F, which is required for cap-dependent translation. Infection of cells by poliovirus results in a...

X-ray structure of the human hyperplastic discs protein: An ortholog of the C-terminal domain of poly(A)-binding protein

Deo, Rahul C., Sonenberg, Nahum, Burley, Stephen K.

The poly(A)-binding protein (PABP) recognizes the 3′ mRNA poly(A) tail and plays an essential role in eukaryotic translation initiation and mRNA stabilization/degradation. PABP is a modular...

The target of rapamycin (TOR) proteins

Raught, Brian, Gingras, Anne-Claude, Sonenberg, Nahum

Rapamycin potently inhibits downstream signaling from the target of rapamycin (TOR) proteins. These evolutionarily conserved protein kinases coordinate the balance between protein synthesis and...

FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse

Hentges, Kathryn E., Sirry, Baheya, Gingeras, Anne-Claude, Sarbassov, Dos, Sonenberg, Nahum, Sabatini, David, ...

The FKBP-12-rapamycin associated protein (FRAP, also known as mTOR and RAFT-1) is a member of the phosphoinositide kinase related kinase family. FRAP has serine/threonine kinase activity and mediates...

Eukaryotic Translation Initiation Factor 4AIII (eIF4AIII) Is Functionally Distinct from eIF4AI and eIF4AII

Li, Qiyu, Imataka, Hiroaki, Morino, Shigenobu, Rogers, George W., Richter-Cook, Nancy J., Merrick, William C., ...

Eukaryotic initiation factor 4A (eIF4A) is an RNA-dependent ATPase and ATP-dependent RNA helicase that is thought to melt the 5′ proximal secondary structure of eukaryotic mRNAs to facilitate...

Eukaryotic Translation Initiation Factor 4E (eIF4E) Binding Site and the Middle One-Third of eIF4GI Constitute the Core Domain for Cap-Dependent Translation, and the C-Terminal One-Third Functions as a Modulatory Region

Morino, Shigenobu, Imataka, Hiroaki, Svitkin, Yuri V., Pestova, Tatyana V., Sonenberg, Nahum

The mammalian eukaryotic initiation factor 4GI (eIF4GI) may be divided into three roughly equal regions; an amino-terminal one-third (amino acids [aa] 1 to 634), which contains the poly(A) binding...

Poliovirus 2A Protease Induces Apoptotic Cell Death

Goldstaub, Dan, Gradi, Alessandra, Bercovitch, Zippi, Grosmann, Zehava, Nophar, Yaron, Luria, Sylvie, ...

A cell line was generated that expresses the poliovirus 2A protease in an inducible manner. Tightly controlled expression was achieved by utilizing the muristerone A-regulated expression system. Upon...

Eap1p, a Novel Eukaryotic Translation Initiation Factor 4E-Associated Protein in Saccharomyces cerevisiae

Cosentino, Gregory P., Schmelzle, Tobias, Haghighat, Ashkan, Helliwell, Stephen B., Hall, Michael N., Sonenberg, Nahum

Ribosome binding to eukaryotic mRNA is a multistep process which is mediated by the cap structure [m7G(5′)ppp(5′)N, where N is any nucleotide] present at the 5′ termini of all cellular (with...

Dual Interactions of the Translational Repressor Paip2 with Poly(A) Binding Protein

Khaleghpour, Kianoush, Kahvejian, Avak, De Crescenzo, Gregory, Roy, Guylaine, Svitkin, Yuri V., Imataka, Hiroaki, ...

The cap structure and the poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This effect is mediated by a direct interaction of eukaryotic initiation factor 4G and poly(A)...

Translational Silencing of Ceruloplasmin Requires the Essential Elements of mRNA Circularization: Poly(A) Tail, Poly(A)-Binding Protein, and Eukaryotic Translation Initiation Factor 4G

Mazumder, Barsanjit, Seshadri, Vasudevan, Imataka, Hiroaki, Sonenberg, Nahum, Fox, Paul L.

Ceruloplasmin (Cp) is a glycoprotein secreted by the liver and monocytic cells and probably plays roles in inflammation and iron metabolism. We showed previously that gamma interferon (IFN-γ)...

Eukaryotic Initiation Factor 4GII (eIF4GII), but Not eIF4GI, Cleavage Correlates with Inhibition of Host Cell Protein Synthesis after Human Rhinovirus Infection

Svitkin, Yuri V., Gradi, Alessandra, Imataka, Hiroaki, Morino, Shigenobu, Sonenberg, Nahum

For many members of the Picornaviridae family, infection of cells results in a shutoff of host protein synthesis. For rhinoviruses and enteroviruses, the shutoff has been explained in part by the...

Translational Homeostasis: Eukaryotic Translation Initiation Factor 4E Control of 4E-Binding Protein 1 and p70 S6 Kinase Activities

Khaleghpour, Kianoush, Pyronnet, Stéphane, Gingras, Anne-Claude, Sonenberg, Nahum

Eukaryotic translation initiation factor 4E (eIF4E) is the mRNA 5′ cap binding protein, which plays an important role in the control of translation. The activity of eIF4E is regulated by a family...

Rapamycin and Wortmannin Enhance Replication of a Defective Encephalomyocarditis Virus

Svitkin, Yuri V., Hahn, Harry, Gingras, Anne-Claude, Palmenberg, Ann C., Sonenberg, Nahum

Inhibitors of the phosphatidylinositol 3-kinase (PI3 kinase)–FKBP-rapamycin-associated protein (FRAP) pathway, such as rapamycin and wortmannin, induce dephosphorylation and activation of the...

The Murine Double-Stranded RNA-Dependent Protein Kinase PKR Is Required for Resistance to Vesicular Stomatitis Virus

Stojdl, David F., Abraham, Ninan, Knowles, Shane, Marius, Ricardo, Brasey, Ann, Lichty, Brian D., ...

Interferon (IFN)-induced antiviral responses are mediated through a variety of proteins, including the double-stranded RNA-dependent protein kinase PKR. Here we show that fibroblasts derived from...

A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus

Tang, Shao Jun, Reis, Gerald, Kang, Hyejin, Gingras, Anne-Claude, Sonenberg, Nahum, Schuman, Erin M.

Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) that endures for more than an hour requires both...

A Novel Functional Human Eukaryotic Translation Initiation Factor 4G

Gradi, Alessandra, Imataka, Hiroaki, Svitkin, Yuri V., Rom, Eran, Raught, Brian, Morino, Shigenobu, ...

Mammalian eukaryotic translation initiation factor 4F (eIF4F) is a cap-binding protein complex consisting of three subunits: eIF4E, eIF4A, and eIF4G. In yeast and plants, two related eIF4G species...

The major mRNA-associated protein YB-1 is a potent 5′ cap-dependent mRNA stabilizer

Evdokimova, Valentina, Ruzanov, Peter, Imataka, Hiroaki, Raught, Brian, Svitkin, Yuri, Ovchinnikov, Lev P., ...

mRNA silencing and storage play an important role in gene expression under diverse circumstances, such as throughout early metazoan development and in response to many types of environmental stress....

Translational Control of Cell Fate: Availability of Phosphorylation Sites on Translational Repressor 4E-BP1 Governs Its Proapoptotic Potency

Li, Shunan, Sonenberg, Nahum, Gingras, Anne-Claude, Peterson, Mark, Avdulov, Svetlana, Polunovsky, Vitaly A., ...

Translational control has been recently added to well-recognized genomic, transcriptional, and posttranslational mechanisms regulating apoptosis. We previously found that overexpressed eukaryotic...

Paip1 Interacts with Poly(A) Binding Protein through Two Independent Binding Motifs

Roy, Guylaine, De Crescenzo, Gregory, Khaleghpour, Kianoush, Kahvejian, Avak, O'Connor-McCourt, Maureen, Sonenberg, Nahum

The 3′ poly(A) tail of eukaryotic mRNAs plays an important role in the regulation of translation. The poly(A) binding protein (PABP) interacts with eukaryotic initiation factor 4G (eIF4G), a...

Phosphorylation of Eukaryotic Translation Initiation Factor 4E Is Critical for Growth

Lachance, Pascal E. D., Miron, Mathieu, Raught, Brian, Sonenberg, Nahum, Lasko, Paul

Eukaryotic translation initiation factor 4E (eIF4E) binds to the cap structure at the 5′ end of mRNAs and is a critical target for the control of protein synthesis. eIF4E is phosphorylated in many...

Regulation of Protein Synthesis by Hypoxia via Activation of the Endoplasmic Reticulum Kinase PERK and Phosphorylation of the Translation Initiation Factor eIF2α

Koumenis, Constantinos, Naczki, Christine, Koritzinsky, Marianne, Rastani, Sally, Diehl, Alan, Sonenberg, Nahum, ...

Hypoxia profoundly influences tumor development and response to therapy. While progress has been made in identifying individual gene products whose synthesis is altered under hypoxia, little is known...

The Transformation Suppressor Pdcd4 Is a Novel Eukaryotic Translation Initiation Factor 4A Binding Protein That Inhibits Translation

Yang, Hsin-Sheng, Jansen, Aaron P., Komar, Anton A., Zheng, Xiaojing, Merrick, William C., Costes, Sylvain, ...

Pdcd4 is a novel transformation suppressor that inhibits tumor promoter-induced neoplastic transformation and the activation of AP-1-dependent transcription required for transformation. A yeast...

The Leader of Human Immunodeficiency Virus Type 1 Genomic RNA Harbors an Internal Ribosome Entry Segment That Is Active during the G2/M Phase of the Cell Cycle

Brasey, Ann, Lopez-Lastra, Marcelo, Ohlmann, Theophile, Beerens, Nancy, Berkhout, Ben, Darlix, Jean-Luc, ...

The 5′ leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA contains highly structured domains involved in key steps of the viral life cycle. These RNA domains inhibit...

A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes

Nikolcheva, Tania, Pyronnet, Stephane, Chou, Szu-yi, Sonenberg, Nahum, Song, An, Clayberger, Carol, ...

Activation of T lymphocytes by specific antigen triggers a 3- to 7-day maturation process. Terminal differentiation begins late after T cell activation and involves expression of effector genes,...

Human Rhinovirus 2A Proteinase Cleavage Sites in Eukaryotic Initiation Factors (eIF) 4GI and eIF4GII Are Different

Gradi, Alessandra, Svitkin, Yuri V., Sommergruber, Wolfgang, Imataka, Hiroaki, Morino, Shigenobu, Skern, Tim, ...

Several picornaviruses shut down host cellular protein synthesis by proteolytic cleavage of the eukaryotic initiation factor (eIF) 4GI and eIF4GII isoforms. Viral RNA translation is maintained by a...

Cell-Free Synthesis of Encephalomyocarditis Virus

Svitkin, Yuri V., Sonenberg, Nahum

We developed a system for complete replication of encephalomyocarditis virus (EMCV) in a test tube by using an in vitro translation extract from Krebs-2 cells. Efficient virus synthesis occurred in a...

A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5′ cap-binding protein, eIF4E

Dostie, Josée, Ferraiuolo, Maria, Pause, Arnim, Adam, Stephen A., Sonenberg, Nahum

The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in the control of cell growth. eIF4E binds to the mRNA 5′ cap structure m7GpppN (where N is any nucleotide), and...

Serum-stimulated, rapamycin-sensitive phosphorylation sites in the eukaryotic translation initiation factor 4GI

Raught, Brian, Gingras, Anne-Claude, Gygi, Steven P., Imataka, Hiroaki, Morino, Shigenobu, Gradi, Alessandra, ...

The eukaryotic translation initiation factor 4G (eIF4G) proteins play a critical role in the recruitment of the translational machinery to mRNA. The eIF4Gs are phosphoproteins. However, the location...

Signaling from Akt to FRAP/TOR Targets both 4E-BP and S6K in Drosophila melanogaster

Miron, Mathieu, Lasko, Paul, Sonenberg, Nahum

The eIF4E-binding proteins (4E-BPs) interact with translation initiation factor 4E to inhibit translation. Their binding to eIF4E is reversed by phosphorylation of several key Ser/Thr residues. In...

Suppression of cap-dependent translation in mitosis

Pyronnet, Stéphane, Dostie, Josée, Sonenberg, Nahum

Cap-dependent translation is mediated by eIF4F, a protein complex composed of three subunits as follows: eIF4E, which recognizes the mRNA 5′ cap structure; eIF4A, an RNA-helicase; and eIF4G, a...

Hierarchical phosphorylation of the translation inhibitor 4E-BP1

Gingras, Anne-Claude, Raught, Brian, Gygi, Steven P., Niedzwiecka, Anna, Miron, Mathieu, Burley, Stephen K., ...

In most instances, translation is regulated at the initiation phase, when a ribosome is recruited to the 5′ end of an mRNA. The eIF4E-binding proteins (4E-BPs) interdict translation initiation by...

4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway

Gingras, Anne-Claude, Kennedy, Scott G., O’Leary, Maura A., Sonenberg, Nahum, Hay, Nissim

Growth factors and hormones activate protein translation by phosphorylation and inactivation of the translational repressors, the eIF4E-binding proteins (4E-BPs), through a wortmannin- and...

Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism

Gingras, Anne-Claude, Gygi, Steven P., Raught, Brian, Polakiewicz, Roberto D., Abraham, Robert T., Hoekstra, Merl F., ...

The multisubunit eukaryotic translation initiation factor (eIF) 4F recruits 40S ribosomal subunits to the 5′ end of mRNA. The eIF4F subunit eIF4E interacts directly with the mRNA 5′ cap...

The Drosophila Poly(A) Binding Protein-Interacting Protein, dPaip2, Is a Novel Effector of Cell Growth

Roy, Guylaine, Miron, Mathieu, Khaleghpour, Kianoush, Lasko, Paul, Sonenberg, Nahum

The 3′ poly(A) tail of eukaryotic mRNAs and the poly(A) binding protein (PABP) play important roles in the regulation of translation. Recently, a human PABP-interacting protein, Paip2, which...

Capped mRNAs with Reduced Secondary Structure Can Function in Extracts from Poliovirus-Infected Cells

Sonenberg, Nahum, Guertin, Denise, Lee, Kevin A. W.

Extracts from poliovirus-infected HeLa cells were used to study ribosome binding of native and denatured reovirus mRNAs and translation of capped mRNAs with different degrees of secondary structure....

Cleavage of Eukaryotic Translation Initiation Factor 4GII within Foot-and-Mouth Disease Virus-Infected Cells: Identification of the L-Protease Cleavage Site In Vitro

Gradi, Alessandra, Foeger, Nicole, Strong, Rebecca, Svitkin, Yuri V., Sonenberg, Nahum, Skern, Tim, ...

Foot-and-mouth disease virus (FMDV) induces a very rapid inhibition of host cell protein synthesis within infected cells. This is accompanied by the cleavage of the eukaryotic translation initiation...

A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay

Ferraiuolo, Maria A., Lee, Chung-Sheng, Ler, Lian Wee, Hsu, Jeanne L., Costa-Mattioli, Mauro, Luo, Ming-Juan, ...

In eukaryotes, a surveillance mechanism known as nonsense-mediated decay (NMD) degrades the mRNA when a premature-termination codon (PTC) is present. NMD requires translation to read the frame of the...

A Novel Function of the MA-3 Domains in Transformation and Translation Suppressor Pdcd4 Is Essential for Its Binding to Eukaryotic Translation Initiation Factor 4A

Yang, Hsin-Sheng, Cho, Myung-Haing, Zakowicz, Halina, Hegamyer, Glenn, Sonenberg, Nahum, Colburn, Nancy H.

Αn α-helical MA-3 domain appears in several translation initiation factors, including human eukaryotic translation initiation factor 4G (eIF4G) and DAP-5/NAT1/p97, as well as in the tumor...

Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases

Raught, Brian, Peiretti, Franck, Gingras, Anne-Claude, Livingstone, Mark, Shahbazian, David, Mayeur, Greg L, ...

The eucaryotic translation initiation factor 4B (eIF4B) stimulates the helicase activity of the DEAD box protein eIF4A to unwind inhibitory secondary structure in the 5′ untranslated region of...

Selective Modification of Eukaryotic Initiation Factor 4F (eIF4F) at the Onset of Cell Differentiation: Recruitment of eIF4GII and Long-Lasting Phosphorylation of eIF4E

Caron, Sandrine, Charon, Martine, Cramer, Elisabeth, Sonenberg, Nahum, Dusanter-Fourt, Isabelle

mRNA translation is mainly regulated at the level of initiation, a process that involves the synergistic action of the 5′ cap structure and the 3′ poly(A) tail at the ends of eukaryotic mRNA. The...

La Autoantigen Is Necessary for Optimal Function of the Poliovirus and Hepatitis C Virus Internal Ribosome Entry Site In Vivo and In Vitro†

Costa-Mattioli, Mauro, Svitkin, Yuri, Sonenberg, Nahum

Translation of poliovirus and hepatitis C virus (HCV) RNAs is initiated by recruitment of 40S ribosomes to an internal ribosome entry site (IRES) in the mRNA 5′ untranslated region. Translation...

UNR, a new partner of poly(A)-binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant

Chang, Tsung-Cheng, Yamashita, Akio, Chen, Chyi-Ying A., Yamashita, Yukiko, Zhu, Wenmiao, Durdan, Simon, ...

Messenger RNA decay mediated by the c-fos major protein coding-region determinant of instability (mCRD) is a useful system for studying translationally coupled mRNA turnover. Among the five...

Resistance to Vesicular Stomatitis Virus Infection Requires a Functional Cross Talk between the Eukaryotic Translation Initiation Factor 2α Kinases PERK and PKR

Baltzis, Dionissios, Qu, Li-Ke, Papadopoulou, Stavroula, Blais, Jaime D., Bell, John C., Sonenberg, Nahum, ...

Phosphorylation of the alpha (α) subunit of the eukaryotic translation initiation factor 2 (eIF2) leads to the inhibition of protein synthesis in response to diverse stress conditions, including...

Translational Repression Mediates Activation of Nuclear Factor Kappa B by Phosphorylated Translation Initiation Factor 2

Deng, Jing, Lu, Phoebe D., Zhang, Yuhong, Scheuner, Donalyn, Kaufman, Randal J., Sonenberg, Nahum, ...

Numerous stressful conditions activate kinases that phosphorylate the alpha subunit of translation initiation factor 2 (eIF2α), thus attenuating mRNA translation and activating a gene expression...

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

Kahvejian, Avak, Svitkin, Yuri V., Sukarieh, Rami, M'Boutchou, Marie-Noël, Sonenberg, Nahum

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′...

Complete Translation of the Hepatitis C Virus Genome In Vitro: Membranes Play a Critical Role in the Maturation of All Virus Proteins except for NS3

Svitkin, Yuri V., Pause, Arnim, Lopez-Lastra, Marcelo, Perreault, Sandra, Sonenberg, Nahum

We developed an in vitro translation extract from Krebs-2 cells that translates the entire open reading frame of the hepatitis C virus (HCV) strain H77 and properly processes the viral protein...

Fibronectin controls cap-dependent translation through β1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways

Gorrini, Chiara, Loreni, Fabrizio, Gandin, Valentina, Sala, Leonardo A., Sonenberg, Nahum, Marchisio, Pier Carlo, ...

Fibronectin (FN) is a major matrix protein involved in multiple processes. Little is known about how adhesion to FN affects the translational machinery. We show that in fibroblasts adhesion to FN...

Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation

Bordeleau, Marie-Eve, Matthews, James, Wojnar, Joanna M., Lindqvist, Lisa, Novac, Olivia, Jankowsky, Eckhard, ...

RNA helicases are the largest group of enzymes in eukaryotic RNA metabolism. The DEXD/H-box putative RNA helicases form the helicase superfamily II, whose members are defined by seven highly...

Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP

Tettweiler, Gritta, Miron, Mathieu, Jenkins, Mark, Sonenberg, Nahum, Lasko, Paul F.

eIF4E, the mRNA 5′ cap-binding protein, is regulated by its binding protein (4E-BP), a downstream target of phosphatidylinositol-3-OH kinase [PI(3)K] signaling. We show that Drosophila 4E-BP...

Structural basis of ligand recognition by PABC, a highly specific peptide-binding domain found in poly(A)-binding protein and a HECT ubiquitin ligase

Kozlov, Guennadi, De Crescenzo, Gregory, Lim, Nadia S, Siddiqui, Nadeem, Fantus, Daniel, Kahvejian, Avak, ...

The C-terminal domain of poly(A)-binding protein (PABC) is a peptide-binding domain found in poly(A)-binding proteins (PABPs) and a HECT (homologous to E6-AP C-terminus) family E3 ubiquitin ligase....

The protein kinase PKR: a molecular clock that sequentially activates survival and death programs

Donzé, Olivier, Deng, Jing, Curran, Joseph, Sladek, Robert, Picard, Didier, Sonenberg, Nahum

Cell death and survival play a key role in the immune system as well as during development. The control mechanisms that balance cell survival against cell death are not well understood. Here we...

Eukaryotic Translation Initiation Factor 4E Availability Controls the Switch between Cap-Dependent and Internal Ribosomal Entry Site-Mediated Translation†

Svitkin, Yuri V., Herdy, Barbara, Costa-Mattioli, Mauro, Gingras, Anne-Claude, Raught, Brian, Sonenberg, Nahum

Translation of m7G-capped cellular mRNAs is initiated by recruitment of ribosomes to the 5′ end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a heterotrimeric complex comprised...

Akt-Mediated YB-1 Phosphorylation Activates Translation of Silent mRNA Species

Evdokimova, Valentina, Ruzanov, Peter, Anglesio, Michael S., Sorokin, Alexey V., Ovchinnikov, Lev P., Buckley, Jonathan, ...

YB-1 is a broad-specificity RNA-binding protein that is involved in regulation of mRNA transcription, splicing, translation, and stability. In both germinal and somatic cells, YB-1 and related...

Phosphorylation of eIF4E attenuates its interaction with mRNA 5′ cap analogs by electrostatic repulsion: Intein-mediated protein ligation strategy to obtain phosphorylated protein

ZUBEREK, JOANNA, WYSLOUCH-CIESZYNSKA, ALEKSANDRA, NIEDZWIECKA, ANNA, DADLEZ, MICHAL, STEPINSKI, JANUSZ, AUGUSTYNIAK, WOJCIECH, ...

Phosphorylation of the eukaryotic initiation factor eIF4E in response to mitogenic stimuli and cytokines is implicated in the regulation of the initiation step of translation. It still remains...

RNA aptamers to initiation factor 4A helicase hinder cap-dependent translation by blocking ATP hydrolysis

OGURO, AKIHIRO, OHTSU, TAKASHI, SVITKIN, YURI V., SONENBERG, NAHUM, NAKAMURA, YOSHIKAZU

The mammalian translation initiation factor 4A (eIF4A) is a prototype member of the DEAD-box RNA helicase family that couples ATPase activity to RNA binding and unwinding. In the crystal form, eIF4A...

High affinity RNA for mammalian initiation factor 4E interferes with mRNA-cap binding and inhibits translation

MOCHIZUKI, KIYOTAKA, OGURO, AKIHIRO, OHTSU, TAKASHI, SONENBERG, NAHUM, NAKAMURA, YOSHIKAZU

The eukaryotic translation initiation factor 4F (eIF4F) consists of three polypeptides (eIF4A, eIF4G, and eIF4E) and is responsible for recruiting ribosomes to mRNA. eIF4E recognizes the mRNA...

Regulation of poly(A) binding protein function in translation: Characterization of the Paip2 homolog, Paip2B

Berlanga, Juan José, Baass, Alexis, Sonenberg, Nahum

The 5′ cap and 3′ poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding...

Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2

Le Bacquer, Olivier, Petroulakis, Emmanuel, Paglialunga, Sabina, Poulin, Francis, Richard, Denis, Cianflone, Katherine, ...

The most common pathology associated with obesity is insulin resistance, which results in the onset of type 2 diabetes mellitus. Several studies have implicated the mammalian target of rapamycin...

Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control

Koritzinsky, Marianne, Magagnin, Michaël G, Van Den Beucken, Twan, Seigneuric, Renaud, Savelkouls, Kim, Dostie, Josée, ...

Hypoxia has recently been shown to activate the endoplasmic reticulum kinase PERK, leading to phosphorylation of eIF2α and inhibition of mRNA translation initiation. Using a quantitative assay, we...

RNA aptamers to mammalian initiation factor 4G inhibit cap-dependent translation by blocking the formation of initiation factor complexes

Miyakawa, Shin, Oguro, Akihiro, Ohtsu, Takashi, Imataka, Hiroaki, Sonenberg, Nahum, Nakamura, Yoshikazu

Eukaryotic translation initiation factor 4G (eIF4G) plays a crucial multimodulatory role in mRNA translation and decay by interacting with other translation factors and mRNA-associated proteins. In...

Antiviral effect of the mammalian translation initiation factor 2α kinase GCN2 against RNA viruses

Berlanga, Juan J, Ventoso, Iván, Harding, Heather P, Deng, Jing, Ron, David, Sonenberg, Nahum, ...

In mammals, four different protein kinases, heme-regulated inhibitor, double-stranded RNA-dependent protein kinase (PKR), general control non-derepressible-2 (GCN2) and PKR-like endoplasmic reticulum...

Poly(A) binding protein (PABP) homeostasis is mediated by the stability of its inhibitor, Paip2

Yoshida, Madoka, Yoshida, Kaori, Kozlov, Guennadi, Lim, Nadia S, De Crescenzo, Gregory, Pang, Zhiyu, ...

The poly(A)-binding protein (PABP) is a unique translation initiation factor in that it binds to the mRNA 3′ poly(A) tail and stimulates recruitment of the ribosome to the mRNA at the 5′ end....

The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity

Shahbazian, David, Roux, Philippe P, Mieulet, Virginie, Cohen, Michael S, Raught, Brian, Taunton, Jack, ...

The eukaryotic translation initiation factor 4B (eIF4B) plays a critical role in recruiting the 40S ribosomal subunit to the mRNA. In response to insulin, eIF4B is phosphorylated on Ser422 by S6K in...

Weak binding affinity of human 4EHP for mRNA cap analogs

Zuberek, Joanna, Kubacka, Dorota, Jablonowska, Agnieszka, Jemielity, Jacek, Stepinski, Janusz, Sonenberg, Nahum, ...

Ribosome recruitment to the majority of eukaryotic mRNAs is facilitated by the interaction of the cap binding protein, eIF4E, with the mRNA 5′ cap structure. eIF4E stimulates translation through...

Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?▿

Burgui, Idoia, Yángüez, Emilio, Sonenberg, Nahum, Nieto, Amelia

Influenza virus mRNAs bear a short capped oligonucleotide sequence at their 5′ ends derived from the host cell pre-mRNAs by a “cap-snatching” mechanism, followed immediately by a common viral...

A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay

Ferraiuolo, Maria A., Basak, Sanjukta, Dostie, Josee, Murray, Elizabeth L., Schoenberg, Daniel R., Sonenberg, Nahum

4E-transporter (4E-T) is one of several proteins that bind the mRNA 5′cap-binding protein, eukaryotic initiation factor 4E (eIF4E), through a conserved binding motif. We previously showed that 4E-T...

Nuclear Eukaryotic Initiation Factor 4e (Eif4e) Colocalizes with Splicing Factors in Speckles

Dostie, Josée, Lejbkowicz, Flavio, Sonenberg, Nahum

The eukaryotic initiation factor 4E (eIF4E) plays a pivotal role in the control of protein synthesis. eIF4E binds to the mRNA 5′ cap structure, m7GpppN (where N is any nucleotide) and promotes...

Stimulation of picornavirus replication by the poly(A) tail in a cell-free extract is largely independent of the poly(A) binding protein (PABP)

Svitkin, Yuri V., Costa-Mattioli, Mauro, Herdy, Barbara, Perreault, Sandra, Sonenberg, Nahum

Picornavirus infectivity is dependent on the RNA poly(A) tail, which binds the poly(A) binding protein (PABP). PABP was reported to stimulate viral translation and RNA synthesis. Here, we studied...

Reconstitution reveals the functional core of mammalian eIF3

Masutani, Mamiko, Sonenberg, Nahum, Yokoyama, Shigeyuki, Imataka, Hiroaki

Eukaryotic translation initiation factor (eIF)3 is the largest eIF (∼650 kDa), consisting of 10–13 different polypeptide subunits in mammalian cells. To understand the role of each subunit, we...

Vesicular Stomatitis Virus Oncolysis of T Lymphocytes Requires Cell Cycle Entry and Translation Initiation▿ †

Oliere, Stephanie, Arguello, Meztli, Mesplede, Thibault, Tumilasci, Vanessa, Nakhaei, Peyman, Stojdl, David, ...

Vesicular stomatitis virus (VSV) is a candidate oncolytic virus that replicates and induces cell death in cancer cells while sparing normal cells. Although defects in the interferon antiviral...

Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53

Lee, Chung-Han, Inoki, Ken, Karbowniczek, Magdalena, Petroulakis, Emmanuel, Sonenberg, Nahum, Henske, Elizabeth Petri, ...

Miscoordination of growth and proliferation with the cellular stress response can lead to tumorigenesis. Mammalian target of rapamycin (mTOR), a central cell growth controller, is highly activated in...

The Dynamics of Mammalian P Body Transport, Assembly, and Disassembly In Vivo

Aizer, Adva, Brody, Yehuda, Ler, Lian Wee, Sonenberg, Nahum, Singer, Robert H., Shav-Tal, Yaron

Exported mRNAs are targeted for translation or can undergo degradation by several decay mechanisms. The 5′→3′ degradation machinery localizes to cytoplasmic P bodies (PBs). We followed the...

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

Rong, Liwei, Livingstone, Mark, Sukarieh, Rami, Petroulakis, Emmanuel, Gingras, Anne-Claude, Crosby, Katherine, ...

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the...

Role of 3′UTRs in the Translation of mRNAs Regulated by Oncogenic eIF4E—A Computational Inference

Santhanam, Arti N., Bindewald, Eckart, Rajasekhar, Vinagolu K., Larsson, Ola, Sonenberg, Nahum, Colburn, Nancy H., ...

Eukaryotic cap-dependent mRNA translation is mediated by the initiation factor eIF4E, which binds mRNAs and stimulates efficient translation initiation. eIF4E is often overexpressed in human cancers....

Poly(A)-Binding Protein-Interacting Protein 1 Binds to Eukaryotic Translation Initiation Factor 3 To Stimulate Translation▿

Martineau, Yvan, Derry, Mélanie C., Wang, Xiaoshan, Yanagiya, Akiko, Berlanga, Juan José, Shyu, Ann-Bin, ...

Poly(A)-binding protein (PABP) stimulates translation initiation by binding simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation factor 4G (eIF4G). PABP activity is regulated...

Requirement of RNA Binding of Mammalian Eukaryotic Translation Initiation Factor 4GI (eIF4GI) for Efficient Interaction of eIF4E with the mRNA Cap▿ †

Yanagiya, Akiko, Svitkin, Yuri V., Shibata, Shoichiro, Mikami, Satoshi, Imataka, Hiroaki, Sonenberg, Nahum

Eukaryotic mRNAs possess a 5′-terminal cap structure (cap), m7GpppN, which facilitates ribosome binding. The cap is bound by eukaryotic translation initiation factor 4F (eIF4F), which is composed...