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
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84937438216&partnerID=40&md5=0e18638c757d404f31fea1ecdbb5e157
Notes:	Export Date: 2 September 2015 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/79866