Regulation and dysregulation of 3′UTR-mediated translational control
Section snippets
The GAIT system as archetype for 3′UTR-mediated translational control and its modulation
Recognition and binding of proteins or protein complexes to defined sequence or structural RNA elements in the mRNA 3′UTR is a common translational control mechanism (Figure 1). This mechanism is generally directed by stimulus-dependent posttranslational modifications that regulate protein–protein interactions and complex assembly, as well as the RNA-binding properties of these assemblages. Recent attention has focused on an additional layer of complexity in which the processes involved in
Translational control by 3′UTR-targeting miRNA
microRNAs (miRNAs) are 20-nt to 23-nt, noncoding RNAs that can target mRNA [12], DNA [13], and even protein [14], to regulate gene expression at both transcriptional and posttranscriptional levels. miRNAs bind complementary sequences, most often in the 3′UTR of target mRNAs, to alter expression by regulating either mRNA decay or translation. A ribosome profiling study pointed to mRNA decay, rather than translational silencing, as the dominant mechanism for miRNA-mediated inhibition of gene
3′UTR-mediated translational control in disease and therapeutics
Experimental and clinical studies have suggested that 3′UTR-mediated translational control has a critical role in regulating gene expression in cancer and other pathological states (Table 1). Phosphorylation of a 3′UTR-binding protein was recently shown to significantly impact transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT), a critical early step in tumorigenesis. The newly recognized BAT (TGF-β-activated translation) complex, consisting of hnRNP E1 and
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
P.L.F was supported by NIH grants P01 HL029582, P01 HL076491, and R01 GM086430, A.A. by a National Center Scientist Development Grant 10SDG3930003 from the American Heart Association, and P.Y. by a fellowship from the American Heart Association, Great Rivers Affiliate. Owing to space limitations, combined with remarkable growth in this burgeoning research area, we were not able to include all, or even most, recent discoveries about this topic; we apologize to the authors whose important work
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