Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy.
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.
Ni, T; Yang, Y; Hafez, D; Yang, W; Kiesewetter, K; Wakabayashi, Y; Ohler, U; Peng, W; Zhu, J
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