Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets

By Nahum Sonenberg, A. Hinnebusch. Cell, 2009

3,293 citations recorded by the source corpus.

Translational control in eukaryotic cells is critical for gene regulation during nutrient deprivation and stress, development and differentiation, nervous system function, aging, and disease. We describe recent advances in our understanding of the molecular structures and biochemical functions of the translation initiation machinery and summarize key strategies that mediate general or gene-specific translational control, particularly in mammalian systems.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/24fc2a94d681c1a8923c34ce3c22acc07500251c

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Citations in the corpus

N6-methyladenosine Modulates Messenger RNA Translation Efficiency (2015, positive): “Global translation regulation is typically achieved by modulating both the activity of translation initiation factors and the availability of ribosomes (Hershey et al., 2012; Sonenberg and Hinnebusch, 2009).”
Eukaryotic stress granules: the ins and outs of translation. (2009, background): “Genetic and biochemical studies have identified eIF5 as a component of 48S complexes (Sonenberg and Hinnebusch, 2009), and eIF5 is required for 48S complex assembly, at least in yeast (Asano et al., 2000).”
Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster (2010, background): “However, under stress, such as lack of nutrients or growth factors, and in hypoxia, cap-independent translation increases (Sonenberg and Hinnebusch, 2009), allowing a switch to synthesis of other proteins, such as growth factors and heat shock proteins (Baird et al., 2006), which enables the cell…”
Studies on the role of helix 69 of 23S rRNA in the factor-dependent stages of translation initiation, elongation, and termination (2011, background): “…intricacy that is catalyzed by more than ten protein factors, including helicases, GTPases and RNA-binding proteins (Kapp and Lorsch 2004; Sonenberg and Hinnebusch 2009; Myasnikov et al. 2009), it is considerably simpler in bacteria where only three initiation factors – IF1, IF2 and IF3…”
Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes (2011, background): “Translation of uORFs can modulate the expression of the downstream protein-coding gene in response to global (Sonenberg and Hinnebusch, 2009) or gene-specific regulatory signals (Medenbach et al.”
Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP (2010, background): “Gene expression in eukaryotes is extensively controlled at the posttranscriptional level by RNA-binding proteins (RBPs) and ribonucleoprotein complexes (RNPs) modulating the maturation, stability, transport, editing and translation of RNA transcripts (Martin and Ephrussi, 2009; Moore and Proudfoot, ”
Angiogenin-induced tRNA fragments inhibit translation initiation (2011, background): “Under conditions of nutrient stress, dephosphorylated 4E-BP displaces eIF4G from eIF4E to inhibit protein synthesis (Sonenberg and Hinnebusch, 2009).”
THE MECHANISM OF EUKARYOTIC TRANSLATION INITIATION AND PRINCIPLES OF ITS REGULATION (2010, background): “Many of the better understood examples conform to the generic model shown in Box 2 (for specific individual examples, see Ref”
In brief (2011, neutral): “The best-characterized substrates of mTORC1 are S6K and 4E-BP via which mTORC1 controls translation (Sonenberg and Hinnebusch, 2009). mTORC2 consists of mTOR, rictor, mSIN1, mLST8, and PRR5/PRR5L (also known as protor1 and 2) and is insensitive to rapamycin, although long-term rapamycin treatment…”
Ribosome mediated specificity in Hox mRNA translation and vertebrate tissue patterning (2011, positive): “Our current understanding of translational regulation has been guided, to a large extent, by studies of early invertebrate development where decisive events occur prior to the initiation of zygotic transcription and are solely directed by translational control of pre-existing maternal mRNAs (Kuerste”
Ribosome profiling reveals pervasive translation outside of annotated protein-coding genes. (2014, background): “For example, AUG codons are depleted in many 50 UTRs, as they interfere with translation of the downstream protein-coding sequence, though this interference is exploited as a regulatory mechanism controlling the expression of genes such as Atf4 (Sonenberg and Hinnebusch, 2009).”