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

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

SUBMITTER: Ni T

PROVIDER: S-EPMC3848854 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Ni Ting T Yang Yanqin Y Hafez Dina D Yang Wenjing W Kiesewetter Kurtis K Wakabayashi Yoshi Y Ohler Uwe U Peng Weiqun W Zhu Jun J

BMC genomics 20130911

<h4>Background</h4>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.<h4>Results</h4>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 ...[more]

PMID: 24025092

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Project description:BackgroundRibosomal proteins (RPs) have about 2000 pseudogenes in the human genome. While anecdotal reports for RP pseudogene transcription exists, it is unclear to what extent these pseudogenes are transcribed. The RP pseudogene transcription is difficult to identify in microarrays due to potential cross-hybridization between transcripts from the parent genes and pseudogenes. Recently, transcriptome sequencing (RNA-seq) provides an opportunity to ascertain the transcription of pseudogenes. A challenge for pseudogene expression discovery in RNA-seq data lies in the difficulty to uniquely identify reads mapped to pseudogene regions, which are typically also similar to the parent genes.ResultsHere we developed a specialized pipeline for pseudogene transcription discovery. We first construct a "composite genome" that includes the entire human genome sequence as well as mRNA sequences of real ribosomal protein genes. We then map all sequence reads to the composite genome, and only exact matches were retained. Moreover, we restrict our analysis to strictly defined mappable regions and calculate the RPKM values as measurement of pseudogene transcription levels. We report evidences for the transcription of RP pseudogenes in 16 human tissues. By analyzing the Human Body Map 2.0 study RNA-sequencing data using our pipeline, we identified that one ribosomal protein (RP) pseudogene (PGOHUM-249508) is transcribed with RPKM 170 in thyroid. Moreover, three other RP pseudogenes are transcribed with RPKM > 10, a level similar to that of the normal RP genes, in white blood cell, kidney, and testes, respectively. Furthermore, an additional thirteen RP pseudogenes are of RPKM > 5, corresponding to the 20-30 percentile among all genes. Unlike ribosomal protein genes that are constitutively expressed in almost all tissues, RP pseudogenes are differentially expressed, suggesting that they may contribute to tissue-specific biological processes.ConclusionsUsing a specialized bioinformatics method, we identified the transcription of ribosomal protein pseudogenes in human tissues using RNA-seq data.

Dataset Information

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

Publications

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

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