Cigarette smoking-associated isoform switching and 3' UTR lengthening via alternative polyadenylation.
Genomics
; 113(6): 4184-4195, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34763026
ABSTRACT
Cigarette smoking induces a profound transcriptomic and systemic inflammatory response. Previous studies have focused on gene level differential expression of smoking, but the genome-wide effects of smoking on alternative isoform regulation have not yet been described. We conducted RNA sequencing in whole-blood samples of 454 current and 767 former smokers in the COPDGene Study, and we analyzed the effects of smoking on differential usage of isoforms and exons. At 10% FDR, we detected 3167 differentially expressed genes, 945 differentially used isoforms and 160 differentially used exons. Isoform switch analysis revealed widespread 3' UTR lengthening associated with cigarette smoking. The lengthening of these 3' UTRs was consistent with alternative usage of distal polyadenylation sites, and these extended 3' UTR regions were significantly enriched with functional sequence elements including microRNA and RNA-protein binding sites. These findings warrant further studies on alternative polyadenylation events as potential biomarkers and novel therapeutic targets for smoking-related diseases.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Poliadenilación
/
Fumar Cigarrillos
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
Genomics
Asunto de la revista:
GENETICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos