Identification of microprotein-coding intronic polyadenylation isoforms and function in genotoxic anticancer drug response.

ABSTRACT:

Background

Many transcript isoforms generated by intronic polyadenylation (IPA) encode isoforms of canonical proteins. Microproteins are an emerging class of small proteins translated from small open reading frames (sORFs) in noncoding RNAs and mRNAs, but their production by IPA isoforms is unknown.

Results

Here, by crossing 3'-seq, Ribo-Seq, and mass-spectrometry data, we identify 297 genes with a microprotein-coding IPA isoform terminating in a 5'UTR intron (coined miP-5'UTR-IPA isoform). By 3'-seq and long-read RNA-seq analyses in lung cancer cells treated with cisplatin, a DNA-cross-linking anticancer drug, we find that cisplatin globally favors the expression of (miP-5'UTR-)IPA isoforms relative to full-length mRNAs, mainly by decreasing the latter through an inhibition

SUBMITTER: Devaux A 

PROVIDER: S-EPMC12548281 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature