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, 50 (4), 158-159

Non-canonical Targets Play an Important Role in microRNA Stability Control Mechanisms

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Non-canonical Targets Play an Important Role in microRNA Stability Control Mechanisms

June Hyun Park et al. BMB Rep.

Abstract

MicroRNAs (miRNAs) regulate gene expression by guiding the Argonaute (Ago)-containing RNA-induced silencing complex (RISC) to specific target mRNA molecules. It is well established that miRNAs are stabilized by Ago proteins, but the molecular features that trigger miRNA destabilization from Ago proteins remain largely unknown. To explore the molecular mechanisms of how targets affect the stability of miRNAs in human Ago (hAgo) proteins, we employed an in vitro system that consisted of a minimal hAgo2-RISC in HEK293T cell lysates. Surprisingly, we found that miRNAs are drastically destabilized by binding to seedless, non-canonical targets. We showed that miRNAs are destabilized at their 3' ends during this process, which is largely attributed to the conformational flexibility of the L1-PAZ domain. Based on these results, we propose that non-canonical targets may play an important regulatory role in controlling the stability of miRNAs, instead of being regulated by miRNAs. [BMB Reports 2017; 50(4): 158-159].

Figures

Fig. 1
Fig. 1
Proposed reaction mechanisms of non-canonical targets in the regulation of miRNA stability in human Ago proteins. miRNAs bind to non-canonical targets with low affinities because of mismatches in the seed region. Upon an extensive 3′ pairing between miRNAs and their targets, the 3′ ends of miRNAs are released from the PAZ domain, and this, in turn, leads to destabilization of miRNAs from Ago proteins.

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