Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape

• Published in: Molecular cell Vol. 84; no. 8; pp. 1475 - 1495.e18
• Main Authors: Boddu, Prajwal C., Gupta, Abhishek K., Roy, Rahul, De La Peña Avalos, Bárbara, Olazabal-Herrero, Anne, Neuenkirchen, Nils, Zimmer, Joshua T., Chandhok, Namrata S., King, Darren, Nannya, Yasuhito, Ogawa, Seishi, Lin, Haifan, Simon, Matthew D., Dray, Eloise, Kupfer, Gary M., Verma, Amit, Neugebauer, Karla M., Pillai, Manoj M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.04.2024
• Subjects: Animals; Chromatin - genetics; co-transcriptional splicing; DNA damage response; Humans; Mice; Mutation; Neoplasms; Phosphoproteins - genetics; Phosphoproteins - metabolism; R-loops; RNA polymerase II; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; RNA Splicing - genetics; RNA Splicing Factors - genetics; RNA Splicing Factors - metabolism; SF3B1; Sin3/HDAC; spliceosome; transcription; U2AF1; WDR5; transcription; co-transcriptional splicing; DNA damage response; WDR5; U2AF1; Sin3/HDAC; spliceosome; R-loops; SF3B1; RNA polymerase II

Transcription and splicing of pre-messenger RNA are closely coordinated, but how this functional coupling is disrupted in human diseases remains unexplored. Using isogenic cell lines, patient samples, and a mutant mouse model, we investigated how cancer-associated mutations in SF3B1 alter transcript...