Steering research on mRNA splicing in cancer towards clinical translation

Berget, S. M., Moore, C. & Sharp, P. A. Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proc. Natl Acad. Sci. USA 74, 3171–3175 (1977).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chow, L. T., Gelinas, R. E., Broker, T. R. & Roberts, R. J. An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell 12, 1–8 (1977).

Article  CAS  PubMed  Google Scholar 

Pan, Q., Shai, O., Lee, L. J., Frey, B. J. & Blencowe, B. J. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40, 1413–1415 (2008).

Article  CAS  PubMed  Google Scholar 

Wang, E. T. et al. Alternative isoform regulation in human tissue transcriptomes. Nature 456, 470–476 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kjer-Hansen, P. & Weatheritt, R. J. The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts. Nat. Struct. Mol. Biol. 30, 1844–1856 (2023).

Article  CAS  PubMed  Google Scholar 

Marasco, L. E. & Kornblihtt, A. R. The physiology of alternative splicing. Nat. Rev. Mol. Cell Biol. 24, 242–254 (2023).

Article  CAS  PubMed  Google Scholar 

Boise, L. H. et al. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74, 597–608 (1993).

Article  CAS  PubMed  Google Scholar 

Cascino, I., Fiucci, G., Papoff, G. & Ruberti, G. Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing. J. Immunol. 154, 2706–2713 (1995).

Article  CAS  PubMed  Google Scholar 

Ueda, H. et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423, 506–511 (2003).

Article  CAS  PubMed  Google Scholar 

Li, X. et al. A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation. Nat. Cell Biol. 18, 561–571 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Han, H. et al. MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature 498, 241–245 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bradley, R. K. & Anczukow, O. RNA splicing dysregulation and the hallmarks of cancer. Nat. Rev. Cancer 23, 135–155 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Climente-Gonzalez, H., Porta-Pardo, E., Godzik, A. & Eyras, E. The functional impact of alternative splicing in cancer. Cell Rep. 20, 2215–2226 (2017).

Article  CAS  PubMed  Google Scholar 

Jayasinghe, R. G. et al. Systematic analysis of splice-site-creating mutations in cancer. Cell Rep. 23, 270–281.e3 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12, 31–46 (2022).

Article  CAS  PubMed  Google Scholar 

Berg, P., Baltimore, D., Brenner, S., Roblin, R. O. & Singer, M. F. Summary statement of the Asilomar conference on recombinant DNA molecules. Proc. Natl Acad. Sci. USA 72, 1981–1984 (1975).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Papaemmanuil, E. et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N. Engl. J. Med. 365, 1384–1395 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yoshida, K. et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478, 64–69 (2011).

Article  CAS  PubMed  Google Scholar 

Graubert, T. A. et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat. Genet. 44, 53–57 (2011).

Article  PubMed  PubMed Central  Google Scholar 

Wang, L. et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N. Engl. J. Med. 365, 2497–2506 (2011). Together with Papaemmanuil et al. (2011) and Yoshida et al. (2011), this work reveals that, in haematologic malignancies, multiple splicing factors accumulate mutations at rates comparable with those of well-established cancer drivers.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seiler, M. et al. Somatic mutational landscape of splicing factor genes and their functional consequences across 33 cancer types. Cell Rep. 23, 282–296.e4 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alsafadi, S. et al. Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage. Nat. Commun. 7, 10615 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Darman, R. B. et al. Cancer-associated SF3B1 hotspot mutations induce cryptic 3′ splice site selection through use of a different branch point. Cell Rep. 13, 1033–1045 (2015).

Article  CAS  PubMed  Google Scholar 

Brooks, A. N. et al. A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events. PLoS ONE 9, e87361 (2014). This study is one of the first to establish direct associations between splicing factor mutations in cancer and alterations in splicing events.

Article  PubMed  PubMed Central  Google Scholar 

Ilagan, J. O. et al. U2AF1 mutations alter splice site recognition in hematological malignancies. Genome Res. 25, 14–26 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, E. et al. SRSF2 mutations contribute to myelodysplasia by mutant-specific effects on exon recognition. Cancer Cell 27, 617–630 (2015). This study documents the specificity in the downstream effects of splicing factor mutations.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, S., Benbarche, S. & Abdel-Wahab, O. Splicing factor mutations in hematologic malignancies. Blood 138, 599–612 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inoue, D. et al. Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition. Nat. Genet. 53, 707–718 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chathoth, K. T., Barrass, J. D., Webb, S. & Beggs, J. D. A splicing-dependent transcriptional checkpoint associated with prespliceosome formation. Mol. Cell 53, 779–790 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin, S., Coutinho-Mansfield, G., Wang, D., Pandit, S. & Fu, X. D. The splicing factor SC35 has an active role in transcriptional elongation. Nat. Struct. Mol. Biol. 15, 819–826 (2008).

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