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3' Uridylation Confers miRNAs with Non-canonical Target Repertoires

  1. Author:
    Yang,Acong
    Bofill De Ros,Xavier
    Shao, Tie-Juan
    Jiang, Minjie
    Li, Katherine
    Villanueva,Patricia
    Dai,Lisheng
    Gu,Shuo

  2. Author Address

    RNA Mediated Gene Regulation Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., RNA Mediated Gene Regulation Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China., RNA Mediated Gene Regulation Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: shuo.gu@nih.gov.,
    1. Year: 2019
    2. Date: Aug 8
    3. Epub Date: 2019 05 25
  2. Journal: Molecular cell
    1. 75
    2. 3
    3. Pages: 511-522.e4
  4. Type of Article: Article
  5. ISSN: 1097-2765
  1. Abstract:

    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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.molcel.2019.05.014
  3. PMID: 31178353
  4. View record in Web of Science®
  5. WOS: 000480342200011
  6. PII : S1097-2765(19)30386-7

Library Notes

  1. Fiscal Year: FY2018-2019
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