RT Journal Article
SR Electronic
T1 Transcript isoform differences across human tissues are predominantly driven by alternative start and termination sites of transcription
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 127894
DO 10.1101/127894
A1 Alejandro Reyes
A1 Wolfgang Huber
YR 2017
UL http://biorxiv.org/content/early/2017/04/17/127894.abstract
AB Most human genes have multiple transcription start and polyadenylation sites, as well as alternatively spliced exons. While transcript isoform diversity contributes to shape cellular specificity, it is currently unclear what is the balance of contributions from alternative splicing compared to alternative start and termination sites of transcription. Here, we address this question by analyzing data from the Genotype-Tissue Expression Project. We found tissue-dependent usage of exons for around one-half of expressed genes. Although tissue-dependent splicing was frequent among untranslated exons, it explained less than half of the differences in exon usage across tissues, suggesting that most of these differences were driven by alternative transcription start and termination sites. Analysis of the FANTOMProject data confirmed widespread tissue-dependent usage of alternative transcriptional start sites. Our analysis highlights alternative initiation and termination sites of transcription as the main drivers of isoform diversity across tissues. We also show that most tissue-dependent splicing is unlikely to have consequences at the proteome level.