Selective suppression of the splicing-mediated MicroRNA pathway by the terminal uridyltransferase Tailor Journal Article

Authors: Bortolamiol-Becet, D.; Hu, F.; Jee, D.; Wen, J.; Okamura, K.; Lin, C. J.; Ameres, S. L.; Lai, E. C.
Article Title: Selective suppression of the splicing-mediated MicroRNA pathway by the terminal uridyltransferase Tailor
Abstract: Several terminal uridyltransferases (TUTases) are known to modulate small RNA biogenesis and/or function via diverse mechanisms. Here, we demonstrate that Drosophila splicing-derived pre-miRNAs (mirtrons) are efficiently modified by the previously uncharacterized TUTase, Tailor. Tailor is necessary and sufficient for mirtron hairpin uridylation, and this modification inhibits mirtron biogenesis. Genome-wide analyses demonstrate that mirtrons are dominant Tailor substrates, and three features contribute to substrate specificity. First, reprogramming experiments show Tailor preferentially identifies splicing-derived miRNAs. Second, invitro tests indicate Tailor prefers substrate hairpins over mature miRNAs. Third, Tailor exhibits sequence preference for 3'-terminal AG, a defining mirtron characteristic. Our work supports the notion that Tailor preferentially suppresses biogenesis of mirtrons, an evolutionarily adventitious pre-miRNA substrate class. Moreover, we detect preferential activity of Tailor on 3'-G canonical pre-miRNAs, and specific depletion of such loci from the pool of conserved miRNAs. Thus, Tailor activity may have had collateral impact on shaping populations of canonical miRNAs. © 2015 Elsevier Inc.
Keywords: nonhuman; microrna; drosophila; in vitro study; inhibition kinetics; enzyme specificity; rna splicing; biogenesis; nuclear reprogramming; article; hexose 1 phosphate uridylyltransferase
Journal Title: Molecular Cell
Volume: 59
Issue: 2
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2015-07-16
Start Page: 217
End Page: 228
Language: English
DOI: 10.1016/j.molcel.2015.05.034
PROVIDER: scopus
PMCID: PMC4517475
PUBMED: 26145174
Notes: Export Date: 2 September 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Eric C Lai
    141 Lai
  2. Jiayu Wen
    11 Wen
  3. David   Jee
    7 Jee
  4. Fuqu   Hu
    5 Hu
  5. Ching-Jung   Lin
    6 Lin