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BMB Rep. 2017 Apr;50(4):158-159.

Non-canonical targets play an important role in microRNA stability control mechanisms.

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Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea.
Department of Agricultural Biotechnology; Research Institute of Agriculture and Life Sciences; and Plant Genomics and Breeding Institute, Seoul National University, Seoul 08826, Korea.


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].

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