Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing.

Authors:
Jan Attig
Jan Attig
UCL Institute of Neurology
United Kingdom
Federico Agostini
Federico Agostini
Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra (UPF)
Spain
Clare Gooding
Clare Gooding
University of Cambridge
United Kingdom
Anob M Chakrabarti
Anob M Chakrabarti
Royal Brompton Hospital
London | United Kingdom
Aarti Singh
Aarti Singh
Maulana Azad Institute of Dental Sciences
India
Nejc Haberman
Nejc Haberman
UCL Institute of Neurology
Julian A Zagalak
Julian A Zagalak
Institute of Pharmaceutical Sciences
Switzerland
Warren Emmett
Warren Emmett
University College London Genetics Institute

Cell 2018 Aug 2;174(5):1067-1081.e17. Epub 2018 Aug 2.

The Francis Crick Institute, Midland Road 1, Kings Cross, London NW1 1AT, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. Electronic address:

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. VIDEO ABSTRACT.

Abstract Video

LINE-ing Up to Influence Splicing / Cell, August 23, 2018 (Vol. 174, Issue 5)


Source: Cell Press

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Source
http://dx.doi.org/10.1016/j.cell.2018.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108849PMC

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August 2018
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