First Author | Yang A | Year | 2019 |
Journal | Mol Cell | Volume | 75 |
Issue | 3 | Pages | 511-522.e4 |
PubMed ID | 31178353 | Mgi Jnum | J:281587 |
Mgi Id | MGI:6357336 | Doi | 10.1016/j.molcel.2019.05.014 |
Citation | Yang A, et al. (2019) 3' Uridylation Confers miRNAs with Non-canonical Target Repertoires. Mol Cell 75(3):511-522.e4 |
abstractText | Many microRNAs (miRNAs) exist alongside abundant miRNA isoforms (isomiRs), most of which arise from post-maturation sequence modifications such as 3' uridylation. However, the ways in which these sequence modifications affect miRNA function remain poorly understood. Here, using human miR-27a in cell lines as a model, we discovered that a nonfunctional target site unable to base-pair extensively with the miRNA seed sequence can regain function when an upstream adenosine is able to base-pair with a post-transcriptionally added uridine in the miR-27a tail. This tail-U-mediated repression (TUMR) is abolished in cells lacking the uridylation enzymes TUT4 and TUT7, indicating that uridylation alters miRNA function by modulating target recognition. We identified a set of non-canonical targets in human cells that are specifically regulated by uridylated miR-27a. We provide evidence that TUMR expands the targets of other endogenous miRNAs. Our study reveals a function of uridylated isomiRs in regulating non-canonical miRNA targets. |