PLX004651

GSE121327: 3 Uridylation Expands miRNA Target Repertoire

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

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 have 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 for uridylated isomiRs in regulating non-canonical miRNA targets.; SOURCE: Shuo Gu (shuo.gu@nih.gov) - RNA Biology Lab National Cancer Institute