Transcriptomic analysis reveals regulation of adipogenesis via long non-coding RNA, alternative splicing, and alternative polyadenylation.
RNA, Long Noncoding
/ genetics
Alternative Splicing
Adipogenesis
/ genetics
Humans
Polyadenylation
Gene Expression Profiling
Adipocytes
/ metabolism
3' Untranslated Regions
MicroRNAs
/ genetics
Transcriptome
Gene Expression Regulation
RNA-Binding Proteins
/ metabolism
Computational Biology
/ methods
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 Jul 2024
23 Jul 2024
Historique:
received:
28
01
2024
accepted:
15
07
2024
medline:
24
7
2024
pubmed:
24
7
2024
entrez:
23
7
2024
Statut:
epublish
Résumé
Obesity is characterized by dysregulated adipogenesis that leads to increased number and/or size of adipocytes. Understanding the molecular mechanisms governing adipogenesis is therefore key to designing therapeutic interventions against obesity. In our study, we analyzed 3'-end sequencing data that we generated from human preadipocytes and adipocytes, as well as previously published RNA-seq datasets, to elucidate mechanisms of regulation via long non-coding RNA (lncRNA), alternative splicing (AS) and alternative polyadenylation (APA). We discovered lncRNAs that have not been previously characterized but may be key regulators of white adipogenesis. We also detected 100 AS events and, using motif enrichment analysis, identified RNA binding proteins (RBPs) that could mediate exon skipping-the most prevalent AS event. In addition, we show that usage of alternative poly(A) sites in introns or 3'-UTRs of key adipogenesis genes leads to isoform diversity, which can have significant biological consequences on differentiation efficiency. We also identified RBPs that may modulate APA and defined how 3'-UTR APA can regulate gene expression through gain or loss of specific microRNA binding sites. Taken together, our bioinformatics-based analysis reveals potential therapeutic avenues for obesity through manipulation of lncRNA levels and the profile of mRNA isoforms via alternative splicing and polyadenylation.
Identifiants
pubmed: 39043790
doi: 10.1038/s41598-024-67648-9
pii: 10.1038/s41598-024-67648-9
doi:
Substances chimiques
RNA, Long Noncoding
0
3' Untranslated Regions
0
MicroRNAs
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16964Subventions
Organisme : NIH HHS
ID : R01 GM101010-01A1
Pays : United States
Informations de copyright
© 2024. The Author(s).
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