Heteromeric RNP assembly at LINEs controls lineage-specific RNA processing
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Published version
Author(s)
Type
Journal Article
Abstract
Long mammalian introns make it challenging for the RNA processing machinery to identify exons accurately. We find that LINE-derived sequences (LINEs) contribute to this selection by recruiting dozens of RNA-binding proteins (RBPs) to introns. This includes MATR3, which promotes binding of PTBP1 to multivalent binding sites within LINEs. Both RBPs repress splicing and 3′ end processing within and around LINEs. Notably, repressive RBPs preferentially bind to evolutionarily young LINEs, which are located far from exons. These RBPs insulate the LINEs and the surrounding intronic regions from RNA processing. Upon evolutionary divergence, changes in RNA motifs within LINEs lead to gradual loss of their insulation. Hence, older LINEs are located closer to exons, are a common source of tissue-specific exons, and increasingly bind to RBPs that enhance RNA processing. Thus, LINEs are hubs for the assembly of repressive RBPs and also contribute to the evolution of new, lineage-specific transcripts in mammals.
Date Issued
2018-08-23
Date Acceptance
2018-07-01
Citation
Cell, 2018, 174 (5), pp.1067-1081.e17
ISSN
0092-8674
Publisher
Elsevier BV
Start Page
1067
End Page
1081.e17
Journal / Book Title
Cell
Volume
174
Issue
5
Copyright Statement
© 2018 The Authors. Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Subjects
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2018-08-02