1532-P: Alternative Polyadenylation in Key Metabolic Tissues from Individuals with Type 2 Diabetes

by sugaradmin



Introduction and Objective: Type 2 diabetes (T2D) is marked by impaired insulin secretion and action in metabolic organs like adipose tissue and skeletal muscle. Aberrant gene expression contributes to T2D. Alternative polyadenylation (APA) alters gene expression by producing mRNA isoforms with variable 3’ UTR lengths. The 3’ UTR interacts with trans-factors, affecting mRNA stability, translation, and localization. This study investigates APA and APA-associated gene expression changes in T2D.Methods: RNA-seq data were downloaded from GEO. APA quantifications used DaPars2, which infers APA dynamics. Differentially expressed genes were identified with a Wilcoxon-Sum test, and pathways analyzed using DAVID and Gene Ontology.Results: Using DaPars2, we analyzed RNA-seq from 152 ND and 66 T2D islets. There are 5,217 genes with longer 3’ UTRs and 1,083 genes with shorter 3’ UTRs. Pathway analysis links longer 3’ UTR genes to intracellular protein transport/folding and ER-to-Golgi transport. Genes with shorter 3’ UTRs are associated with insulin responses/receptor signaling and mRNA processing. In epicardial adipose tissue (38 ND, 41 T2D), 317 genes have longer 3’ UTRs linked to cytoplasmic translation, triglyceride metabolism, and localization. Meanwhile, 1,018 genes have shorter 3’ UTRs tied to transcription regulation by RNA Polymerase II, protein transport, cell proliferation, and miRNA regulation. In lateralis skeletal muscle (28 ND, 34 T2D samples), 317 genes have elongated 3’ UTRs and 1,018 have shorter 3’ UTRs. Longer 3’ UTR genes are linked to cytoplasmic translation, triglyceride metabolism, and localization. Shorter 3’ UTR genes are tied to transcription regulation by RNA Polymerase II, protein transport, cell proliferation, and miRNA regulation.Conclusion: APA analysis of metabolic organs reveals genes with APA and differential expression link to processes contributing to the diabetic phenotype, offering insights into gene regulation and therapeutic targets.

Disclosure

P. Ellsworth: None. Q. Yang: None. J.Q. Dai-Ju: None. Y. Cao: None.

Funding

3R01DK136940-02S15R01DK136940-02



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