Smu1 and RED are required for activation of spliceosomal B complexes assembled on short introns

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  • dc.contributor.author Keiper, Sandra
  • dc.contributor.author Papasaikas, Panagiotis
  • dc.contributor.author Will, Cindy L.
  • dc.contributor.author Valcárcel, J. (Juan)
  • dc.contributor.author Girard, Cyrille
  • dc.contributor.author Lüchrmann, Reinhard
  • dc.date.accessioned 2019-10-28T13:35:48Z
  • dc.date.available 2019-10-28T13:35:48Z
  • dc.date.issued 2019
  • dc.description.abstract Human pre-catalytic spliceosomes contain several proteins that associate transiently just prior to spliceosome activation and are absent in yeast, suggesting that this critical step is more complex in higher eukaryotes. We demonstrate via RNAi coupled with RNA-Seq that two of these human-specific proteins, Smu1 and RED, function both as alternative splicing regulators and as general splicing factors and are required predominantly for efficient splicing of short introns. In vitro splicing assays reveal that Smu1 and RED promote spliceosome activation, and are essential for this step when the distance between the pre-mRNA's 5' splice site (SS) and branch site (BS) is sufficiently short. This Smu1-RED requirement can be bypassed when the 5' and 3' regions of short introns are physically separated. Our observations suggest that Smu1 and RED relieve physical constraints arising from a short 5'SS-BS distance, thereby enabling spliceosomes to overcome structural challenges associated with the splicing of short introns.
  • dc.description.sponsorship Work in the J.V. laboratory was supported by Fundación Botín, Banco de Santander through its Santander Universities Global Division, the European Research Council (ERC AdvG 670146), AGAUR, Spanish Ministry of Economy and Competitiveness (BFU 2014-005153 and BFU 2017 89308-P) and the Centre of Excellence Severo Ochoa. Work in the R.L. laboratory was supported by a grant from the Deutsche Forschungsgemeinschaft SFB 860.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Keiper S, Papasaikas P, Will CL, Valcárcel J, Girard C, Lührmann R. Smu1 and RED are required for activation of spliceosomal B complexes assembled on short introns. Nat Commun. 2019;10(1):3639. DOI: 10.1038/s41467-019-11293-8
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-11293-8
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/42531
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature Communications. 2019;10(1):3639
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-005153
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89308-P
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670146
  • dc.rights © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Genetics
  • dc.subject.keyword Genome informatics
  • dc.subject.keyword RNA
  • dc.subject.keyword RNA splicing
  • dc.title Smu1 and RED are required for activation of spliceosomal B complexes assembled on short introns
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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