Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib.

ABSTRACT: Cellular stresses induce transcription readthrough, whereby RNA polymerase II elongates past a gene's polyadenylation cleavage site without RNA cleavage. Readthrough has been reported in several cancer types. Here, we use long-read sequencing of nascent RNA to quantify transcriptional readthrough in chronic myelogenous leukemia (CML) cells and characterize early responses to the targeted therapeutic, imatinib. We show that the amount, length, and gene-specificity of readthrough increase within 1 hour, while gene expression and alternative splicing alterations emerge later. Strikingly, imatinib-dependent mRNA isoform changes involved "readthrough chimeras", in which exons from an upstream gene are alternatively spliced to exons in a downstream gene. Modifications in mRNA isoforms and chimer

SUBMITTER: Podszywalow-Bartnicka P 

PROVIDER: S-EPMC12637586 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature