Widespread intronic polyadenylation diversifies immune cell transcriptomes

Nat Commun. 2018 Apr 30;9(1):1716. doi: 10.1038/s41467-018-04112-z.


Alternative cleavage and polyadenylation (ApA) is known to alter untranslated region (3'UTR) length but can also recognize intronic polyadenylation (IpA) signals to generate transcripts that lose part or all of the coding region. We analyzed 46 3'-seq and RNA-seq profiles from normal human tissues, primary immune cells, and multiple myeloma (MM) samples and created an atlas of 4927 high-confidence IpA events represented in these cell types. IpA isoforms are widely expressed in immune cells, differentially used during B-cell development or in different cellular environments, and can generate truncated proteins lacking C-terminal functional domains. This can mimic ectodomain shedding through loss of transmembrane domains or alter the binding specificity of proteins with DNA-binding or protein-protein interaction domains. MM cells display a striking loss of IpA isoforms expressed in plasma cells, associated with shorter progression-free survival and impacting key genes in MM biology and response to lenalidomide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Angiogenesis Inhibitors / therapeutic use
  • Case-Control Studies
  • Gene Expression
  • Gene Library
  • Gene Ontology
  • Heavy Chain Disease / genetics*
  • Heavy Chain Disease / immunology
  • Humans
  • Immunoglobulin mu-Chains / genetics*
  • Immunoglobulin mu-Chains / immunology
  • Introns*
  • Lenalidomide / therapeutic use
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Plasma Cells / immunology*
  • Plasma Cells / pathology
  • Polyadenylation*
  • Primary Cell Culture
  • Progression-Free Survival
  • Transcriptome*


  • 3' Untranslated Regions
  • Angiogenesis Inhibitors
  • IGHM protein, human
  • Immunoglobulin mu-Chains
  • Lenalidomide