PUBLICATION

Selective microRNA uridylation by Zcchc6 (TUT7) and Zcchc11 (TUT4)

Authors
Thornton, J.E., Du, P., Jing, L., Sjekloca, L., Lin, S., Grossi, E., Sliz, P., Zon, L.I., Gregory, R.I.
ID
ZDB-PUB-140917-5
Date
2014
Source
Nucleic acids research   42(18): 11777-91 (Journal)
Registered Authors
Jing, Lili, Zon, Leonard I.
Keywords
none
MeSH Terms
  • Animals
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Humans
  • MicroRNAs/chemistry
  • MicroRNAs/metabolism*
  • Nucleotide Motifs
  • RNA Nucleotidyltransferases/antagonists & inhibitors
  • RNA Nucleotidyltransferases/genetics
  • RNA Nucleotidyltransferases/metabolism*
  • Uridine/metabolism*
  • Zebrafish/genetics
PubMed
25223788 Full text @ Nucleic Acids Res.
Abstract
Recent small RNA sequencing data has uncovered 3' end modification of mature microRNAs (miRNAs). This non-templated nucleotide addition can impact miRNA gene regulatory networks through the control of miRNA stability or by interfering with the repression of target mRNAs. The miRNA modifying enzymes responsible for this regulation remain largely uncharacterized. Here we describe the ability for two related terminal uridyl transferases (TUTases), Zcchc6 (TUT7) and Zcchc11 (TUT4), to 3' mono-uridylate a specific subset of miRNAs involved in cell differentiation and Homeobox (Hox) gene control. Zcchc6/11 selectively uridylates these miRNAs in vitro, and we biochemically define a bipartite sequence motif that is necessary and sufficient to confer Zcchc6/11 catalyzed uridylation. Depletion of these TUTases in cultured cells causes the selective loss of 3' mono-uridylation of many of the same miRNAs. Upon TUTase-dependent loss of uridylation, we observe a concomitant increase in non-templated 3' mono-adenylation. Furthermore, TUTase inhibition in Zebrafish embryos causes developmental defects and aberrant Hox expression. Our results uncover the molecular basis for selective miRNA mono-uridylation by Zcchc6/11, highlight the precise control of different 3' miRNA modifications in cells and have implications for miRNA and Hox gene regulation during development.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes