Developmental Cell
Volume 20, Issue 3, 15 March 2011, Pages 388-396
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Short Article
Target-Mediated Protection of Endogenous MicroRNAs in C. elegans

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Summary

MicroRNAs (miRNAs) are tightly regulated through transcriptional and posttranscriptional mechanisms, including degradation by nucleases. Here, we report that in C. elegans, target mRNAs can protect their cognate miRNAs from degradation in vivo. We show that the let-7(n2853) mutation destabilizes the mature let-7 miRNA by impairing this protection. Moreover, presence of a cognate target or depletion of the xrn-1 (XRN1) or xrn-2 (XRN2/Rat1p) exoribonucleases enforces accumulation of certain miRNA passenger (miR) strands. Thus, following biased miRNA strand loading into Argonaute, elimination of nonfunctional RNAs can further refine miRNA strand selection. Conversely, by aligning the levels of miRNAs with those of their targets, the opposing activities of mature miRNA degradation and target-mediated miRNA protection (TMMP) may enable dynamic expression of either mature strand of a pre-miRNA, and evolution of miRNAs. Thus, it seems that mRNAs are more than inert targets and function with miRNAs in a network of mutual regulation.

Highlights

C. elegans XRN-1 and XRN-2 degrade miRNA guide and selected passenger strands ► Target mRNA-mediated miRNA protection (TMMP) stabilizes mature miRNAs in vivo ► XRN-1 and XRN-2 proofread miRNA strand selection after RISC loading ► Degradation and TMMP may facilitate miRNA evolution and dynamic expression

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