College of Life Sciences, Beijing Normal University, Beijing 100875, PR China.
EMBO Rep. 2013 Jun;14(6):568-76. doi: 10.1038/embor.2013.53. Epub 2013 Apr 26.
MicroRNAs (miRNAs) post-transcriptionally repress gene expression via the miRNA-induced silencing complex (miRISC), which includes miRNA, Argonaute and a GW182 family member. Here we show that in Caenorhabditis elegans, miRNA-mediated gene silencing is modulated by macroautophagy, a lysosome-mediated degradation process. Loss of autophagy activity suppresses developmental defects caused by partially impaired silencing of miRNA targets including the let-7 family and lsy-6. The C. elegans GW182 homolog AIN-1 is itself selectively degraded by autophagy and colocalizes with the p62 homolog SQST-1 in autophagy mutants. Thus, autophagy activity modulates miRNA-mediated gene silencing and degrades a core miRISC component.
微 RNA(miRNAs)通过 miRNA 诱导的沉默复合物(miRISC)进行转录后基因表达抑制,该复合物包括 miRNA、Argonaute 和一个 GW182 家族成员。在这里,我们表明在秀丽隐杆线虫中,miRNA 介导的基因沉默受巨自噬调节,巨自噬是一种溶酶体介导的降解过程。自噬活性的丧失抑制了 miRNA 靶基因部分沉默引起的发育缺陷,包括 let-7 家族和 lsy-6。秀丽隐杆线虫的 GW182 同源物 AIN-1 本身被自噬选择性降解,并在自噬突变体中与 p62 同源物 SQST-1 共定位。因此,自噬活性调节 miRNA 介导的基因沉默并降解核心 miRISC 成分。