Widespread intronic polyadenylation diversifies immune cell transcriptomes Journal Article


Authors: Singh, I.; Lee, S. H.; Sperling, A. S.; Samur, M. K.; Tai, Y. T.; Fulciniti, M.; Munshi, N. C.; Mayr, C.; Leslie, C. S.
Article Title: Widespread intronic polyadenylation diversifies immune cell transcriptomes
Abstract: 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. © 2018 The Author(s).
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-04-30
Start Page: 1716
Language: English
DOI: 10.1038/s41467-018-04112-z
PROVIDER: scopus
PMCID: PMC5928244
PUBMED: 29712909
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Christine Mayr
    14 Mayr
  2. Christina Leslie
    106 Leslie
  3. Irtisha Singh
    8 Singh
  4. Shih-Han Lee
    6 Lee