Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
Open Access
- 20 September 2021
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in RNA
- Vol. 27 (12), 1557-1576
- https://doi.org/10.1261/rna.078935.121
Abstract
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 recapitulate the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.Keywords
Funding Information
- FPI Fellowships from the Spanish Ministry of Economy and Competitiveness
- European Research Council (ERC AdvG 670146)
- AGAUR, Spanish Ministry of Economy and Competitiveness (BFU 2017 89308-P)
- the Centre of Excellence Severo Ochoa
- Spanish Ministry of Science and Innovation to the EMBL partnership and the CERCA Programme/Generalitat de Catalunya
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