Molecular impact of mutations in RNA splicing factors in cancer
Year: 2024
Type: review
Abstract: Somatic mutations in genes encoding components of the RNA splicing machinery occur frequently in multiple forms of cancer. The most frequently mutated RNA splicing factors in cancer impact intronic branch site and 3' splice site recognition. These include mutations in the core RNA splicing factor SF3B1 as well as mutations in the U2AF1/2 heterodimeric complex, which recruits the SF3b complex to the 3' splice site. Additionally, mutations in splicing regulatory proteins SRSF2 and RBM10 are frequent in cancer, and there has been a recent suggestion that variant forms of small nuclear RNAs (snRNAs) may contribute to splicing dysregulation in cancer. Here, we describe molecular mechanisms by which mutations in these factors alter splice site recognition and how studies of this process have yielded new insights into cancer pathogenesis and the molecular regulation of splicing. We also discuss data linking mutant RNA splicing factors to RNA metabolism beyond splicing.
Source: Molecular Cell
Authors: Qian Zhang, Yuxi Ai, Omar Abdel-Wahab
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Awards: G271495716, Targeting an RNA Binding Protein Network in Acute Myeloid Leukemia, Interrogating the minor spliceosome to understand and treat leukemia, Cancer Center Support Grant, The Memorial Sloan Kettering Cancer Center SPORE in Leukemia, Charting the differentiation topology of SF3B1 mutated clonal hematopoiesis (CH) and myelodysplastic syndromes (MDS) via a multi-omics single-cell toolkit, Genetic and molecular basis for SRSF2 mutations in myelodysplasia, Synthetic introns for selective targeting of RNA splicing factor-mutant leukemia
OpenAlex ID: W4401577369