Mechanism of Cytoplasmic mRNA Translation

Browning, Karen S.; Bailey‐Serres, Julia

doi:10.1199/tab.0176

Cited by 190 publications

(247 citation statements)

References 395 publications

(580 reference statements)

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“…To obtain a fuller appreciation of where eIF4F fits into the grand scheme of things, the reader may find one or more of the closing references to reviews useful (72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) …”

Section: Other Complicationsmentioning

confidence: 99%

eIF4F: A Retrospective

Merrick

2015

Journal of Biological Chemistry

149

156

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The original purification of the heterotrimeric eIF4F was published over 30 years ago (Grifo, J. A., Tahara, S. M., Morgan, M. A., Shatkin, A. J., and Merrick, W. C. (1983) J. Biol. Chem. 258, 5804 -5810). Since that time, numerous studies have been performed with the three proteins specifically required for the translation initiation of natural mRNAs, eIF4A, eIF4B, and eIF4F. These have involved enzymatic and structural studies of the proteins and a number of site-directed mutagenesis studies. The regulation of translation exhibited through the mammalian target of rapamycin (mTOR) pathway is predominately seen as the phosphorylation of 4E-BP, an inhibitor of protein synthesis that functions by binding to the cap binding subunit of eIF4F (eIF4E). A hypothesis that requires the disassembly of eIF4F during translation initiation to yield free subunits (eIF4A, eIF4E, and eIF4G) is presented. The Biology of eIF4FThe initial findings in the study of natural mRNA translation reflected the newly discovered m 7 G cap at the 5Ј end of eukaryotic mRNAs (2). mRNAs lacking this structure were translated with less efficiency than mRNAs that contained this structure (3). This unique structure allowed for specific assays or purifications, many established in the laboratory of Dr. Aaron Shatkin with assists from his colleagues. Two of note were the use of m 7 G-Sepharose for affinity purification (4, 5) and the crosslinking of periodate-oxidized mRNAs to proteins (6).The initial application of these methodologies identified two different molecular weight species (about 25,000 and at least 200,000), although the high molecular weight protein contained the small molecular weight component, now known as eIF4E (7). Given the size of several other known translation factors, the question was whether these contained the small molecular weight subunit (notably eIF3 and eIF4B) (8 -11). Ultimate purification of eIF4F indicated that neither of these were correct but that eIF4F would form stable complexes with either, thus being consistent with the eIF4E component tracking with them. At the same time, it was recognized that the 46,000 molecular weight subunit of eIF4F was eIF4A. By physical analysis, eIF4F was a heterotrimeric complex of eIF4A, eIF4E, and eIF4G (1).The next studies were to attempt to identify the functions of the various proteins required specifically for natural mRNA translation (eIF4A, eIF4B, and eIF4F). The characteristics of these three proteins were very different. In the absence of ATP, binding to RNA could only be well demonstrated with eIF4F (Table 1). eIF4A and eIF4F could hydrolyze ATP in the presence of single-stranded RNA, and eIF4B would enhance both of these activities (12). In terms of mechanism, the coupling of the binding of ATP and RNA was realized in recognizing that eIF4A or eIF4F had the ability to unwind duplex RNA. As noted in Table 1, the "strength" of the helicase activity was greater with eIF4F (14).As the ability to determine amino acid sequence from RNA sequence advanced, it was found that there...

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Section: Other Complicationsmentioning

confidence: 99%

eIF4F: A Retrospective

Merrick

2015

Journal of Biological Chemistry

149

156

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“…Due to further protein modifications, higher structures are obtained, which nonprotein components are able to bind to. A final functional form appears as a result of these modifications (Kawaguchi and Bailey-Serres 2002;Phillips 2008;Bock 2013;Browning and Bailey-Serres 2015). Translation initiation efficiency depends on the nucleotides flanking start codon ATG, called TIC (translation initiation context) and on its distance from transcript 5′ end (Koul et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Cis-regulatory elements used to control gene expression in plants

Biłas

Szafran

Hnatuszko-Konka

et al. 2016

Plant Cell Tiss Organ Cult

209

113

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“…The eIF4F complex is composed of eIF4E (the capbinding subunit) and eIF4G (an adaptor protein), to which a variety of accessory proteins bind, including eIF4A, eIF4B, and poly(A)-binding protein (PABP). Plants possess a unique form of the eIF4F complex, eIFiso4F, composed of eIFiso4G and eIFiso4E (Browning and Bailey-Serres, 2015). Numerous combinations of the plant cap-binding and adapter proteins are possible, but there are indications that the different combinations have different affinities for particular mRNAs (Carberry et al, 1991;Ruud et al, 1998;Gallie and Browning, 2001;Mayberry et al, 2009Mayberry et al, , 2011.…”

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confidence: 99%

eIF4A RNA Helicase Associates with Cyclin-Dependent Protein Kinase A in Proliferating Cells and Is Modulated by Phosphorylation

et al. 2016

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Eukaryotic initiation factor 4A (eIF4A) is a highly conserved RNA-stimulated ATPase and helicase involved in the initiation of messenger RNA translation. Previously, we found that eIF4A interacts with cyclin-dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. Here, we show that this interaction occurs only in proliferating cells where the two proteins coassociate with 59-cap-binding protein complexes, eIF4F or the plant-specific eIFiso4F. CDKA phosphorylates eIF4A on a conserved threonine residue (threonine-164) within the RNA-binding motif 1b TPGR. In vivo, a phospho-null (APGR) variant of the Arabidopsis (Arabidopsis thaliana) eIF4A1 protein retains the ability to functionally complement a mutant (eif4a1) plant line lacking eIF4A1, whereas a phosphomimetic (EPGR) variant fails to complement. The phospho-null variant (APGR) rescues the slow growth rate of roots and rosettes, together with the ovule-abortion and late-flowering phenotypes. In vitro, wild-type recombinant eIF4A1 and its phospho-null variant both support translation in cell-free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and also was deficient in ATP hydrolysis and helicase activity. These observations suggest a mechanism whereby CDK phosphorylation has the potential to downregulate eIF4A activity and thereby affect translation.

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Mechanism of Cytoplasmic mRNA Translation

Cited by 190 publications

References 395 publications

eIF4F: A Retrospective

eIF4F: A Retrospective

Cis-regulatory elements used to control gene expression in plants

eIF4A RNA Helicase Associates with Cyclin-Dependent Protein Kinase A in Proliferating Cells and Is Modulated by Phosphorylation

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