Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466: 835-840

Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Nature (Impact Factor: 41.46). 08/2010; 466(7308):835-40. DOI: 10.1038/nature09267
Source: PubMed


MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (>/=84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.

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Available from: Huili Guo, Aug 21, 2014
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    • "Three mechanisms have been described for gene regulation via miRNA (1) translation repression, (2) direct mRNA degradation (III) and miRNA-mediated mRNA decay. Recent data have suggested that the mechanism of repression is predominately via a decrease in mRNA target stability (Guo et al. 2011). miRNA activity and abundance is also regulated on various levels ranging from transcription and processing to target site binding and miRNA stability (Treiber et al. 2012). "
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    • "Noncanonical targets have also been reported, although in much smaller numbers (Lal et al. 2009; Shin et al. 2010; Chi et al. 2012; Loeb et al. 2012; Helwak et al. 2013; Grosswendt et al. 2014). Different studies have reported various degrees of miRNA-induced mRNA destabilization and translational inhibition (Baek et al. 2008; Selbach et al. 2008; Guo et al. 2010; Stadler et al. 2012; Hendrickson et al. 2009; Huntzinger and Izaurralde 2011; Jovanovic et al. 2012; Hausser et al. 2013). A few recent studies have shown that translational inhibition precedes mRNA destabilization (Djuranovic et al. 2012; Bazzini et al. 2012), although a report argued that miRNA induced poly(A)-tail shortening can affect translational repression and mRNA destabilization differently in different developmental stages (Subtelny et al. 2014). "
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    • "miRNAs were initially thought to repress their target proteins with little or no impact on their mRNA levels [77]. However , many studies have recently indicated that mammalian miRNAs may predominantly act by decreasing the target mRNA levels [78]. Although most studies have focused on the ability of miRNAs to silence genes, some recent data also suggest that some miRNAs may also increase protein translation under certain conditions [79]. "
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