Discovery of physiological and cancer-related regulators of 3' UTR processing with KAPAC

Genome Biol. 2018 Mar 28;19(1):44. doi: 10.1186/s13059-018-1415-3.

Abstract

3' Untranslated regions (3' UTRs) length is regulated in relation to cellular state. To uncover key regulators of poly(A) site use in specific conditions, we have developed PAQR, a method for quantifying poly(A) site use from RNA sequencing data and KAPAC, an approach that infers activities of oligomeric sequence motifs on poly(A) site choice. Application of PAQR and KAPAC to RNA sequencing data from normal and tumor tissue samples uncovers motifs that can explain changes in cleavage and polyadenylation in specific cancers. In particular, our analysis points to polypyrimidine tract binding protein 1 as a regulator of poly(A) site choice in glioblastoma.

Keywords: APA; CFIm; Cleavage and polyadenylation; Colon adenocarcinoma; Glioblastoma; HNRNPC; KAPAC; PAQR; PTBP1; Prostate adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Humans
  • Male
  • Nucleotide Motifs
  • Polyadenylation*
  • Polypyrimidine Tract-Binding Protein / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • RNA-Binding Proteins / metabolism
  • Sequence Analysis, RNA*
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • 3' Untranslated Regions
  • RNA-Binding Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • Polypyrimidine Tract-Binding Protein