Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation, but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140, and CHERP, form a tight physical and functionally co...
| Authors: | ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2021 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/52825 |
| Online Access: | http://hdl.handle.net/10230/52825 http://dx.doi.org/10.1261/rna.078935.121 |
| Access Level: | Open access |
| Keyword: | Genètica Cèl·lules -- Proliferació Càncer |
| _version_ | 1878739062162980865 |
|---|---|
| author | Martín García, Elena, 1975- |
| author2 | Vivori, Claudia, 1989- Rogalska, Malgorzata Herrero-Vicente, Jorge Valcárcel, J. (Juan) |
| author2_role | author author author author |
| author_browse | Herrero-Vicente, Jorge Martín García, Elena, 1975- Rogalska, Malgorzata Valcárcel, J. (Juan) Vivori, Claudia, 1989- |
| author_facet | Martín García, Elena, 1975- Vivori, Claudia, 1989- Rogalska, Malgorzata Herrero-Vicente, Jorge Valcárcel, J. (Juan) |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation, but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140, and CHERP, form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell-cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulates the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_ba5bc00aac667b385e82030fadebbd6a |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10230/52825 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | Cold Spring Harbor Laboratory Press (CSHL Press) |
| publisherStr | Cold Spring Harbor Laboratory Press (CSHL Press) |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation Martín García, Elena, 1975- Vivori, Claudia, 1989- Rogalska, Malgorzata Herrero-Vicente, Jorge Valcárcel, J. (Juan) Genètica Cèl·lules -- Proliferació Càncer The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation, but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140, and CHERP, form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell-cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulates the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation. Funding: E.M. and J.H. are recipients of FPI Fellowships from the Spanish Ministry of Economy and Competitiveness.Work in our laboratory has been supported by the European Research Council (ERC AdvG 670146), AGAUR, Spanish Ministry of Economy and Competitiveness (BFU2017-89308-P), and the Centre of Excellence Severo Ochoa. We acknowledge suport from the Spanish Ministry of Science and Innovation to the EMBL partnership and the CERCA Programme/Generalitat de Catalunya Cold Spring Harbor Laboratory Press (CSHL Press) http://hdl.handle.net/10230/52825 http://dx.doi.org/10.1261/rna.078935.121 |
| spellingShingle | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation Martín García, Elena, 1975- Genètica Cèl·lules -- Proliferació Càncer |
| status_str | publishedVersion |
| title | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation |
| title_full | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation |
| title_fullStr | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation |
| title_full_unstemmed | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation |
| title_short | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation |
| title_sort | Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation |
| topic | Genètica Cèl·lules -- Proliferació Càncer |
| topic_facet | Genètica Cèl·lules -- Proliferació Càncer |
| url | http://hdl.handle.net/10230/52825 http://dx.doi.org/10.1261/rna.078935.121 |