Promiscuous splicing-derived hairpins are dominant substrates of tailing-mediated defense of miRNA biogenesis in mammals Journal Article

   

Authors:	Lee, S.; Jee, D.; Srivastava, S.; Yang, A.; Ramidi, A.; Shang, R.; Bortolamiol-Becet, D.; Pfeffer, S.; Gu, S.; Wen, J.; Lai, E. C.
Article Title:	Promiscuous splicing-derived hairpins are dominant substrates of tailing-mediated defense of miRNA biogenesis in mammals
Abstract:	Canonical microRNA (miRNA) hairpins are processed by the RNase III enzymes Drosha and Dicer into ∼22 nt RNAs loaded into an Argonaute (Ago) effector. In addition, splicing generates numerous intronic hairpins that bypass Drosha (mirtrons) to yield mature miRNAs. Here, we identify hundreds of previously unannotated, splicing-derived hairpins in intermediate-length (∼50–100 nt) but not small (20–30 nt) RNA data. Since we originally defined mirtrons from small RNA duplexes, we term this larger set as structured splicing-derived RNAs (ssdRNAs). These associate with Dicer and/or Ago complexes, but generally accumulate modestly and are poorly conserved. We propose they contaminate the canonical miRNA pathway, which consequently requires defense against the siege of splicing-derived substrates. Accordingly, ssdRNAs/mirtrons comprise dominant hairpin substrates for 3′ tailing by multiple terminal nucleotidyltransferases, notably TUT4/7 and TENT2. Overall, the rampant proliferation of young mammalian mirtrons/ssdRNAs, coupled with an inhibitory molecular defense, comprises a Red Queen's race of intragenomic conflict. © 2023 The Author(s)
Keywords:	controlled study; unclassified drug; human cell; microrna; enzyme substrate; rna; mammal; rna structure; argonaute protein; genetic conservation; bioaccumulation; rna splicing; biogenesis; dicer; nucleotidyltransferase; protein rna binding; mirtron; human; article; tutase; intragenomic conflict; cp: molecular biology; ssdrna; structured splicing-derived rna; tent enzyme; structured splicing derived rna; tent2 protein; tut4 protein; tut7 protein
Journal Title:	Cell Reports
Volume:	42
Issue:	2
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2023-02-28
Start Page:	112111
Language:	English
DOI:	10.1016/j.celrep.2023.112111
PUBMED:	36800291
PROVIDER:	scopus
PMCID:	PMC10508058
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85148057920&doi=10.1016%2fj.celrep.2023.112111&partnerID=40&md5=b62cdcc08bc21317fa4d3f0dc628917c
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Eric Lai -- Export Date: 1 March 2023 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/203226