The mechanism of eukaryotic translation initiation and principles of its regulation
TLDR
This work has provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).Abstract:
Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control of gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions in ribosomal initiation complexes, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity (which affects almost all scanning-dependent initiation) and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).read more
Citations
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Gene silencing by microRNAs: contributions of translational repression and mRNA decay.
Eric Huntzinger,Elisa Izaurralde +1 more
TL;DR: This work has shown that microRNAs can induce mRNA degradation in animals and, conversely, translational repression in plants and shed light on the specific mechanisms of target silencing.
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The integrated stress response.
Karolina Pakos-Zebrucka,Izabela Koryga,Katarzyna Mnich,Mila Ljujic,Afshin Samali,Adrienne M. Gorman +5 more
TL;DR: Current understanding of the ISR signaling is reviewed and how it regulates cell fate under diverse types of stress is reviewed.
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A census of human RNA-binding proteins.
TL;DR: This work presents a census of 1,542 manually curated RBPs that are analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression, a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.
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MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship
TL;DR: This work has shown that targets can reciprocally control the level and function of miRNAs, and this has important implications for the use of these RNAs in therapeutic settings.
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Towards a molecular understanding of microRNA-mediated gene silencing
Stefanie Jonas,Elisa Izaurralde +1 more
TL;DR: Understanding of the mechanisms of silencing is enhanced, making it possible to describe in molecular terms a continuum of direct interactions from miRNA target recognition to mRNA deadenylation, decapping and 5′-to-3′ degradation.
References
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Journal ArticleDOI
Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
TL;DR: Recent advances in understanding of the molecular structures and biochemical functions of the translation initiation machinery are described and key strategies that mediate general or gene-specific translational control are summarized, particularly in mammalian systems.
Journal ArticleDOI
Structural features in eukaryotic mRNAs that modulate the initiation of translation.
TL;DR: In higher eukaryotes, translation is modulated at the level of initiation by five aspects of mRNA structure: (i) the m7G cap; (ii) the primary sequence or context surrounding the AUG codon; (iii) the position of the Aug codon, i.e. whether or not it s “first”; (iv) secondary structure both upstream and downstream from the AUU; and (v) leader length.
Journal ArticleDOI
Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells
Krishna M. Vattem,Ronald C. Wek +1 more
TL;DR: The results suggest that the mechanism of translation reinitiation involving uORFs is conserved from yeast to mammals.
Book
Translational control of gene expression
TL;DR: Origins and Principles of Translational Control, Genetic Approaches to Translation Initiation in Saccharomyces cerevisiae, and Programmed translational Frameshifting, Hopping, an
Journal ArticleDOI
Relief of microRNA-Mediated Translational Repression in Human Cells Subjected to Stress
Suvendra N. Bhattacharyya,Regula Habermacher,Ursula Martiné,Ellen I. Closs,Witold Filipowicz +4 more
TL;DR: This work shows that cationic amino acid transporter 1 (CAT-1) mRNA and reporters bearing its 3'UTR can be relieved from the microRNA miR-122-induced inhibition in human hepatocarcinoma cells subjected to different stress conditions and proposes that proteins interacting with the 3'utR will generally act as modifiers altering the potential of miRNAs to repress gene expression.