Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy

BMC Genomics. 2013 Sep 11:14:615. doi: 10.1186/1471-2164-14-615.


Background: Polyadenylation is a key regulatory step in eukaryotic gene expression and one of the major contributors of transcriptome diversity. Aberrant polyadenylation often associates with expression defects and leads to human diseases.

Results: To better understand global polyadenylation regulation, we have developed a polyadenylation sequencing (PA-seq) approach. By profiling polyadenylation events in 13 human tissues, we found that alternative cleavage and polyadenylation (APA) is prevalent in both protein-coding and noncoding genes. In addition, APA usage, similar to gene expression profiling, exhibits tissue-specific signatures and is sufficient for determining tissue origin. A 3' untranslated region shortening index (USI) was further developed for genes with tandem APA sites. Strikingly, the results showed that different tissues exhibit distinct patterns of shortening and/or lengthening of 3' untranslated regions, suggesting the intimate involvement of APA in establishing tissue or cell identity.

Conclusions: This study provides a comprehensive resource to uncover regulated polyadenylation events in human tissues and to characterize the underlying regulatory mechanism.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • Chromosome Mapping
  • Cluster Analysis
  • Gene Library
  • Humans
  • Organ Specificity
  • Polyadenylation*
  • Sequence Analysis, RNA / methods*


  • 3' Untranslated Regions