MicroRNAs (miRNAs) silence target mRNAs by inhibiting translation and subsequently initiating mRNA decay. The mechanism by which miRNAs silence translation is still poorly understood, with a number of competing models proposed. In this issue of The EMBO Journal, Kuzuoğlu‐Öztürk et al (2016) investigated miRNA silencing in human and insect cells. Their data support a model whereby miRNAs inhibit translation initiation. However, in contrast to several recent reports, their data suggest that translational inhibition is independent of 43S ribosomal subunit scanning, eIF4A translation factor activity, and 5′UTR secondary structure.
See also: D Kuzuoğlu-Öztürk et al (June 2016)
MicroRNAs (miRNAs) are a class of short (~21 nt) RNAs that post‐transcriptionally repress gene expression by hybridizing to target mRNAs (Jonas & Izaurralde, 2015). In general, miRNAs inhibit protein synthesis by first repressing mRNA translation and subsequently initiating mRNA deadenylation, decapping, and decay. miRNAs recruit the miRNA‐induced silencing complex (miRISC), a ribonucleoprotein complex composed of a miRNA‐loaded Argonaute (AGO) protein, and the AGO‐interacting protein GW182. GW182 also interacts with the poly(A) binding protein (PABP) and facilitates mRNA deadenylation by recruiting the PAN2–PAN3 and CCR4–NOT deadenylase complexes. While the mechanism by which miRNAs promote mRNA decay is relatively well understood, it is still unclear how miRNAs inhibit translation.
Several early studies pointed to miRNAs inhibiting cap‐dependent translation at the initiation step via an unknown mechanism (Humphreys …
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