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Updated: May 8, 2026

Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy
Ting Ni1, Yanqin Yang, Dina Hafez
1National Heart Lung Blood Institute, National Institutes of Health, Genetics and Development Biology Center, 9000 Rockville Pike, Bethesda, MD, 20892, USA. tingni@fudan.edu.cn.
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.

