Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation.
Elena MartínClaudia VivoriMalgorzata RogalskaJorge Herrero-VicenteJuan ValcárcelPublished in: RNA (New York, N.Y.) (2021)
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.
Keyphrases
- cell cycle
- cell proliferation
- cell cycle arrest
- pi k akt
- cell death
- induced apoptosis
- genome wide
- transcription factor
- endoplasmic reticulum stress
- oxidative stress
- physical activity
- single cell
- mental health
- papillary thyroid
- quality improvement
- bioinformatics analysis
- stem cells
- dna methylation
- mesenchymal stem cells
- signaling pathway
- genome wide analysis