Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28119422&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28119422.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nucleic+Acids+Res 2017 ; 45 (4): 1569-83 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Non-canonical targets destabilize microRNAs in human Argonautes #MMPMID28119422
Park JH; Shin SY; Shin C
Nucleic Acids Res 2017[Feb]; 45 (4): 1569-83 PMID28119422show ga
Although much is known about microRNA (miRNA) biogenesis and the mechanism by which miRNAs regulate their targets, little is known about the regulation of miRNA stability. Mature miRNAs are stabilized by binding to Argonaute (Ago) proteins, the core components of the RNA-induced silencing complex (RISC). Recent studies suggest that interactions between miRNAs and their highly complementary target RNAs promote release of miRNAs from Ago proteins, and this in turn can lead to destabilization of miRNAs. However, the physiological triggers of miRNA destabilization with molecular mechanisms remain largely unknown. Here, using an in vitro system that consists of a minimal human Ago2?RISC in HEK293T cell lysates, we sought to understand how miRNAs are destabilized by their targets. Strikingly, we showed that miRNA destabilization is dramatically enhanced by an interaction with seedless, non-canonical targets. We then showed that this process entails not only unloading of miRNAs from Ago, but also 3? end destabilization of miRNAs occurred within Ago. Furthermore, our mutation analysis indicates that conformational changes in the hinge region of the Ago PAZ domain are likely to be the main driving force of the miRNA destabilization. Our collective results suggest that non-canonical targets may provide a stability control mechanism in the regulation of miRNAs in humans.