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Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing

Attig, J; Agostini, F; Gooding, C; Chakrabarti, AM; Singh, A; Haberman, N; Zagalak, JA; ... Ule, J; + view all (2018) Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing. Cell , 174 (5) 1067-1081.e17. 10.1016/j.cell.2018.07.001. Green open access

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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.

Type: Article
Title: Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2018.07.001
Publisher version: https://doi.org/10.1016/j.cell.2018.07.001
Language: English
Additional information: © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: CLIP, LINE repeats, MATR3, PTBP1, alternative polyadenylation, cryptic exons, evolution, exonogenesis, multivalency, splicing
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/10055156
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