TY - JOUR
T1 - Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'2-UTR landscape across seven tumour types
AU - Xia, Zheng
AU - Donehower, Lawrence A.
AU - Cooper, Thomas A.
AU - Neilson, Joel R.
AU - Wheeler, David A.
AU - Wagner, Eric J.
AU - Li, Wei
N1 - Funding Information:
We would like to thank Benjamin Rodriguez for critical reading of this manuscript and members of the Li laboratory for helpful discussions. This work was partially supported by NIH R01HG007538, CPRIT RP110471 and DOD W81XWH-10-1-0501 (to W.L.), NIH grants CA167752 and CA166274 (to E.J.W.). We gratefully acknowledge the contributions from TCGA Research Network and its TCGA Pan-Cancer Analysis Working Group.
Publisher Copyright:
© 2014 Macmillan Publishers Limited.
PY - 2014
Y1 - 2014
N2 - Alternative polyadenylation (APA) is a pervasive mechanism in the regulation of most human genes, and its implication in diseases including cancer is only beginning to be appreciated. Since conventional APA profiling has not been widely adopted, global cancer APA studies are very limited. Here we develop a novel bioinformatics algorithm (DaPars) for the de novo identification of dynamic APAs from standard RNA-seq. When applied to 358 TCGA Pan-Cancer tumour/normal pairs across seven tumour types, DaPars reveals 1,346 genes with recurrent and tumour-specific APAs. Most APA genes (91%) have shorter 3'2-untranslated regions (3â 2 UTRs) in tumours that can avoid microRNA-mediated repression, including glutaminase (GLS), a key metabolic enzyme for tumour proliferation. Interestingly, selected APA events add strong prognostic power beyond common clinical and molecular variables, suggesting their potential as novel prognostic biomarkers. Finally, our results implicate CstF64, an essential polyadenylation factor, as a master regulator of 3' 2-UTR shortening across multiple tumour types.
AB - Alternative polyadenylation (APA) is a pervasive mechanism in the regulation of most human genes, and its implication in diseases including cancer is only beginning to be appreciated. Since conventional APA profiling has not been widely adopted, global cancer APA studies are very limited. Here we develop a novel bioinformatics algorithm (DaPars) for the de novo identification of dynamic APAs from standard RNA-seq. When applied to 358 TCGA Pan-Cancer tumour/normal pairs across seven tumour types, DaPars reveals 1,346 genes with recurrent and tumour-specific APAs. Most APA genes (91%) have shorter 3'2-untranslated regions (3â 2 UTRs) in tumours that can avoid microRNA-mediated repression, including glutaminase (GLS), a key metabolic enzyme for tumour proliferation. Interestingly, selected APA events add strong prognostic power beyond common clinical and molecular variables, suggesting their potential as novel prognostic biomarkers. Finally, our results implicate CstF64, an essential polyadenylation factor, as a master regulator of 3' 2-UTR shortening across multiple tumour types.
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U2 - 10.1038/ncomms6274
DO - 10.1038/ncomms6274
M3 - Article
C2 - 25409906
AN - SCOPUS:84923366707
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 5274
ER -