Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression Journal Article

Authors: Lianoglou, S.; Garg, V.; Yang, J. L.; Leslie, C. S.; Mayr, C.
Article Title: Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression
Abstract: More than half of human genes use alternative cleavage and polyadenylation (ApA) to generate mRNA transcripts that differ in the lengths of their 3' untranslated regions (UTRs), thus altering the post-transcriptional fate of the message and likely the protein output. The extent of 3' UTR variation across tissues and the functional role of ApA remain poorly understood.We developed a sequencing method called 3'-seq to quantitatively map the 3' ends of the transcriptome of diverse human tissues and isogenic transformation systems. We found that cell typespecific gene expression is accomplished by two complementary programs. Tissue-restricted genes tend to have single 3' UTRs, whereas a majority of ubiquitously transcribed genes generate multiple 3' UTRs. During transformation and differentiation, single-UTR genes change their mRNA abundance levels, while multi-UTR genes mostly change 3' UTR isoform ratios to achieve tissue specificity. However, both regulation programs target genes that function in the same pathways and processes that characterize the new cell type. Instead of finding global shifts in 3' UTR length during transformation and differentiation, we identify tissue-specific groups of multi-UTR genes that change their 3' UTR ratios; these changes in 3' UTR length are largely independent from changes in mRNA abundance. Finally, tissue-specific usage of ApA sites appears to be a mechanism for changing the landscape targetable by ubiquitously expressed microRNAs. © 2013 Lianoglou et al.
Keywords: computational biology; gene regulation; transcriptome analysis; alternative polyadenylation; 3' utr isoform; tissue-specific regulation of gene expression
Journal Title: Genes and Development
Volume: 27
Issue: 21
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2013-11-01
Start Page: 2380
End Page: 2396
Language: English
DOI: 10.1101/gad.229328.113
PROVIDER: scopus
PMCID: PMC3828523
PUBMED: 24145798
Notes: --- - "Export Date: 2 December 2013" - "CODEN: GEDEE" - "Source: Scopus"
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MSK Authors
  1. Christine Mayr
    14 Mayr
  2. Christina Leslie
    106 Leslie
  3. Vidur Garg
    6 Garg
  4. Li   Yang
    3 Yang