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Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing.
Cell. 2018 08 23; 174(5):1067-1081.e17.Cell

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. VIDEO

ABSTRACT

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Authors+Show Affiliations

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: j.attig@ucl.ac.uk.The Francis Crick Institute, Midland Road 1, Kings Cross, London NW1 1AT, UK.Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.The Francis Crick Institute, Midland Road 1, Kings Cross, London NW1 1AT, UK; Department of Genetics, Environment and Evolution, UCL Genetics Institute, Gower Street, London WC1E 6BT, UK.Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Department of Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK.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.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.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; Department of Genetics, Environment and Evolution, UCL Genetics Institute, Gower Street, London WC1E 6BT, UK.Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.The Francis Crick Institute, Midland Road 1, Kings Cross, London NW1 1AT, UK; Department of Genetics, Environment and Evolution, UCL Genetics Institute, Gower Street, London WC1E 6BT, UK; Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan.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: jernej.ule@crick.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media

Language

eng

PubMed ID

30078707

Citation

Attig, Jan, et al. "Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing." Cell, vol. 174, no. 5, 2018, pp. 1067-1081.e17.
Attig J, Agostini F, Gooding C, et al. Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing. Cell. 2018;174(5):1067-1081.e17.
Attig, J., Agostini, F., Gooding, C., Chakrabarti, A. M., Singh, A., Haberman, N., Zagalak, J. A., Emmett, W., Smith, C. W. J., Luscombe, N. M., & Ule, J. (2018). Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing. Cell, 174(5), 1067-e17. https://doi.org/10.1016/j.cell.2018.07.001
Attig J, et al. Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing. Cell. 2018 08 23;174(5):1067-1081.e17. PubMed PMID: 30078707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing. AU - Attig,Jan, AU - Agostini,Federico, AU - Gooding,Clare, AU - Chakrabarti,Anob M, AU - Singh,Aarti, AU - Haberman,Nejc, AU - Zagalak,Julian A, AU - Emmett,Warren, AU - Smith,Christopher W J, AU - Luscombe,Nicholas M, AU - Ule,Jernej, Y1 - 2018/08/02/ PY - 2017/12/02/received PY - 2018/04/23/revised PY - 2018/07/01/accepted PY - 2018/8/7/pubmed PY - 2019/5/14/medline PY - 2018/8/7/entrez KW - CLIP KW - LINE repeats KW - MATR3 KW - PTBP1 KW - alternative polyadenylation KW - cryptic exons KW - evolution KW - exonogenesis KW - multivalency KW - splicing SP - 1067 EP - 1081.e17 JF - Cell JO - Cell VL - 174 IS - 5 N2 - 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. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/30078707/Heteromeric_RNP_Assembly_at_LINEs_Controls_Lineage_Specific_RNA_Processing_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(18)30857-2 DB - PRIME DP - Unbound Medicine ER -