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Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation.

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 recapitulates the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.

SUBMITTER: Martin E

PROVIDER: S-EPMC8594467 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Alternative splicing regulation of cell cycle genes by SPF45/SR140/CHERP complex controls cancer cell proliferation

Project description:SPF45, SR140 and CHERP were knock downed using lentiviral delivery of shRNAs in HeLa cells

2021-07-30 | GSE180892 | GEO

Alternative splicing regulation of cell cycle genes by SPF45/SR140/CHERP complex controls cancer cell proliferation

Project description:Alternative splicing regulation of cell cycle genes by SPF45/SR140/CHERP complex controls cancer cell proliferation

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Mitogen-activated protein kinase phosphorylation of splicing factor 45 (SPF45) regulates SPF45 alternative splicing site utilization, proliferation, and cell adhesion.

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CHERP controls alternative mRNA splicing in human cell line

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2022-06-19 | GSE193399 | GEO

PPIB-regulated alternative splicing of cell cycle genes contributes to the regulation of cell proliferation.

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Regulation of NUMB alternative splicing by RBM5, RBM6 and RBM10 controls cancer cell proliferation (CLIP-Seq)

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