The majority of human mRNAs generate alternative 3′ untranslated regions (UTRs) through various processes, including RNA modifications such as RNA editing, m⁶A methylation, and alternative polyadenylation (APA), with 3’UTR splicing as an emerging mechanism. Multiple factors, ranging from the genome to transcriptome level, regulate these processes and contribute to 3’UTR heterogeneity. Genomic variants in 3’UTR regions as well as aberrant 3’UTR processing alter the transcriptomic landscape and are associated with cancer. Increasing evidence, aided by high-resolution sequencing technologies and large-scale computational analyses, points towards potential crosstalk between these processes, whose deregulation may further contribute to cancer pathogenesis. In-depth characterization of these events will increase our appreciation of their significance and help to drive therapeutic development in this field.

PMID: 36372614      DOI: 10.1016/j.tcb.2022.10.001