A comprehensive map of alternative polyadenylation in African American and European American lung cancer patients.
3' Untranslated Regions
Black or African American
/ genetics
Aged
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ ethnology
Male
Middle Aged
Poly A
/ genetics
Polyadenylation
/ genetics
Prognosis
RNA, Messenger
/ genetics
RNA, Untranslated
/ genetics
United States
White People
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 09 2021
23 09 2021
Historique:
received:
12
10
2020
accepted:
22
07
2021
entrez:
24
9
2021
pubmed:
25
9
2021
medline:
21
10
2021
Statut:
epublish
Résumé
Deciphering the post-transcriptional mechanisms (PTM) regulating gene expression is critical to understand the dynamics underlying transcriptomic regulation in cancer. Alternative polyadenylation (APA)-regulation of mRNA 3'UTR length by alternating poly(A) site usage-is a key PTM mechanism whose comprehensive analysis in cancer remains an important open challenge. Here we use a method and analysis pipeline that sequences 3'end-enriched RNA directly to overcome the saturation limitation of traditional 5'-3' based sequencing. We comprehensively map the APA landscape in lung cancer in a cohort of 98 tumor/non-involved tissues derived from European American and African American patients. We identify a global shortening of 3'UTR transcripts in lung cancer, with notable functional implications on the expression of both coding and noncoding genes. We find that APA of non-coding RNA transcripts (long non-coding RNAs and microRNAs) is a recurrent event in lung cancer and discover that the selection of alternative polyA sites is a form of non-coding RNA expression control. Our results indicate that mRNA transcripts from EAs are two times more likely than AAs to undergo APA in lung cancer. Taken together, our findings comprehensively map and identify the important functional role of alternative polyadenylation in determining transcriptomic heterogeneity in lung cancer.
Identifiants
pubmed: 34556645
doi: 10.1038/s41467-021-25763-5
pii: 10.1038/s41467-021-25763-5
pmc: PMC8460807
doi:
Substances chimiques
3' Untranslated Regions
0
RNA, Messenger
0
RNA, Untranslated
0
Poly A
24937-83-5
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5605Informations de copyright
© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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