Synergistic activation of eIF4A by eIF4B and eIF4G

Nielsen, Klaus; Behrens, Manja A.; He, Yangzi; Oliveira, Cristiano L. P.; Jensen, Lars Sottrup; Hoffmann, Søren Vrønning; Pedersen, Jan Skov; Andersen, Gregers Rom

doi:10.1093/nar/gkq1206

Cited by 67 publications

(92 citation statements)

References 46 publications

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“…Moreover, eIF4G accelerates phosphate release and thereby RNA release. The scaffolding protein eIF4G may therefore act in a catalytic fashion, inducing multiple rounds of formation of eIF4A-eIF4B-RNA 92 , which would also be consistent with the structural and biochemical evidence (FIG. 4).…”

Section: Nuclear Specklessupporting

confidence: 85%

“…In addition, full-length eIF4G might also increase binding of eIF4A to RNA by providing additional RNAbinding sites 85 . A further study indicated that eIF4G promotes the formation of a complex of eIF4A, eIF4B and RNA 92 . Moreover, eIF4G accelerates phosphate release and thereby RNA release.…”

Section: Nuclear Specklesmentioning

confidence: 95%

“…Moreover, the DEAD box protein Ded1 and the non-DEAD box protein DEAH box 29 (DHX29) affect translation of mRNAs with long and structured 5′ UTRs, respectively 96,97 . One alternative, and not mutually exclusive, possibility is that eIF4A induces conformational changes in the translation initiation complex, or that ATPmodulated, transient bindin g to RNA may be necessary for ordered initiation to occur 92 . Defining the mRNA sites to which eIF4A binds might provide insights into its many functions.…”

Section: Nuclear Specklesmentioning

confidence: 99%

“…The cap-binding complex eIF4F is composed of the cap-binding protein eIF4E, the scaffolding protein eIF4G and the translation initiation factor eIF4A. The 40S initiation complex then scans through the 5′ untranslated region for the first AUG initiator codon to begin translation 76,88,92 . Association of programmed cell death 4 (PDCD4) with two molecules of eIF4A (middle) triggers a conformational change that prevents association with eIF4G and thereby inhibits the initiation of translation.…”

Section: Nuclear Specklesmentioning

confidence: 99%

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From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

911

1,019

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Nearly all aspects of RNA metabolism, from transcription and translation to mRNA decay, involve RNA helicases, which are enzymes that use ATP to bind or remodel RNA and RNA-protein complexes (ribonucleoprotein (RNP) complexes) 1 . RNA helicases are found in all three domains of life, and many viruses also encode one or more of these proteins 2,3 . Together with the structurally related DNA helicases that function in replication, recombination and repair, the RNA helicases are classified into superfamilies and families, based on sequence and structural features 3,4 . DEAD box proteins form the largest helicase family, with 37 members in humans and 26 in Saccharomyces cerevisiae 3 , and are characterized by the presence of an Asp-Glu-Ala-Asp (DEAD) motif.DEAD box helicases have central and, in many cases, essential physiological roles in cellular RNA metabolism 5 (FIG. 1). The proteins generally function as part of larger multicomponent assemblies, such as the spliceosom e or the eukaryotic translation initiation machinery 6 . Mutations and deregulation of several DEAD box proteins have been linked to disease states, including cancer 7 . Although all DEAD box proteins contain a structurally highly conserved core with conserved ATP-binding and RNA-binding sites, different proteins have been associated with diverse and seemingly unrelated functions, including the disassembly of RNPs, chaperoning during RNA folding and even stabil ization of protein complexes on RNA 5,6 . How these highly conserved proteins fulfil such an array of different functions has been a long-standing question.Research has now started to illuminate the molecular basis for this functional diversity. In this Review, we summarize how structural data, together with biochemical and biophysical studies, have revealed unexpected modes by which these proteins function. We also discuss how novel molecular and cell biological approaches have better defined the cellular roles of DEAD box helicases. We outline our current view on common structural and mechan istic themes that have emerged, and on physical models of how these 'unusual' RNA helicases work.Structures of DEAD box RNA helicases A number of structural studies have universally shown that members of the DEAD box family contain a highly conserved helicase core that harbours the binding sites for ATP and RNA 3,4,8 . The core is surrounded by variable auxiliary domains, which are thought to be critical for the diverse functions of these enzymes.Structure of the helicase core. DEAD box proteins belong to helicase superfamily 2 (SF2) 2 . Similarly to all SF2 helicases, DEAD box proteins are built around a highly conserved helicase core of two virtually identical domains that resemble the bacterial recombination protein recombinase A (RecA) 3,4,8 (FIG. 2a,b). Within this helicase core, at least 12 characteristic sequence motifs are located at conserved positions (FIG. 2a,b). Some of these motifs are conserved across the entire SF2 family, whereas others are found only in the DEAD box family 3 ....

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Section: Nuclear Specklessupporting

confidence: 85%

Section: Nuclear Specklesmentioning

confidence: 95%

Section: Nuclear Specklesmentioning

confidence: 99%

Section: Nuclear Specklesmentioning

confidence: 99%

See 2 more Smart Citations

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

911

1,019

View full text Add to dashboard Cite

show abstract

“…This conclusion is supported by the finding that PDCD4 inhibits cap-dependent, but not cap-independent, mRNA translation (10,33). The RNA helicase activity of eIF4A is stimulated not only through its association with eIF4G, but also upon interaction with eIF4B (34,35). In part, the stimulation occurs through an eIF4B-induced enhancement of the affinity of eIF4A for both RNA and ATP.…”

Section: Discussionmentioning

confidence: 87%

Role of p70S6K1-mediated Phosphorylation of eIF4B and PDCD4 Proteins in the Regulation of Protein Synthesis

Dennis

Jefferson

Kimball

2012

Journal of Biological Chemistry

109

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Background: mTORC1 directly phosphorylates p70S6K1 and the 4E-BPs. Results: Although necessary, eIF4E⅐eIF4G complex formation was insufficient for sustaining global rates of protein synthesis. Conclusion: p70S6K1-mediated phosphorylation of eIF4B and PDCD4 also was required to optimally stimulate protein synthesis. Significance: Both eIF4E⅐eIF4G complex formation and activation of p70S6K1 individually stimulate global rates of protein synthesis.

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Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

Kim

Lee

et al. 2020

Hematological Oncology

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Identification of gene fusion is an essential part in the management of patients with acute leukemia, not only for diagnosis but also in predicting the treatment outcome and selecting appropriate treatment. Adopting next-generation sequencing (NGS) technology for identification of gene fusion in patients with acute leukemia can be a good alternative to conventional tests. In the present study, the NGS RNA fusion gene panel test was applied to diagnostic samples of patients with acute leukemia to identify fusion genes more efficiently. Among 134 patients with acute leukemia, 53 gene fusions were detected in 52 patients. In addition to the recurrent gene fusions specified in the WHO diagnostic criteria, 11 rare or novel gene fusions were identified. Of those, two were gene fusions associated with Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), two were novel gene fusions, three were gene fusions with novel partner genes, and six were rare gene fusions from previous reports. We confirmed the clinical utility of the NGS test in identifying clinically significant gene fusions such as gene fusions involving KMT2A that has a large number of partners. Notably, Ph-like ALL-associated gene fusions could be easily identified despite the wide variety of genes involved. The results from the present study may contribute toward a better understanding of the genomic landscape of acute leukemia as well as patient management. K E Y W O R D Sacute leukemia, next-generation sequencing, RNA gene fusion detection

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Synergistic activation of eIF4A by eIF4B and eIF4G

Cited by 67 publications

References 46 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

Role of p70S6K1-mediated Phosphorylation of eIF4B and PDCD4 Proteins in the Regulation of Protein Synthesis

Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

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