Alternative Polyadenylation Results in mRNA Transcript Instability in Gestational Diabetes Mellitus

Area of Science:

• Genomics
• Reproductive Medicine
• Molecular Biology

Background:

• Gestational diabetes mellitus (GDM) is a significant pregnancy complication.
• Selective polyadenylation (APA) is a crucial post-transcriptional regulation process affecting gene expression.
• Dysregulation of APA may contribute to various diseases, including metabolic disorders.

Purpose of the Study:

• To investigate APA characteristics in GDM placental tissues.
• To identify genes and pathways affected by APA alterations in GDM.
• To explore the role of APA in GDM pathogenesis.

Main Methods:

• Poly(A) site sequencing (PAS-seq) and high-throughput transcriptome sequencing (RNA-seq) were performed on placental tissues from GDM and healthy pregnant women.
• Differential gene expression and variable 3'UTR analysis were conducted.
• Gene Ontology (GO) and pathway analyses were employed for functional enrichment.

Main Results:

• 202 transcript terminal site (TTS) loci showed differential polyadenylation in GDM, with 103 shortened and 99 delayed.
• 57 genes exhibited statistically significant TTS changes (P<0.05).
• VCPIP1 and LGR4 were identified as differentially expressed genes; enriched pathways included cell development, signaling, and transcriptional regulation.

Conclusions:

• Aberrant APA processes are likely involved in the development and progression of GDM.
• Genes with significant TTS alterations may serve as potential biomarkers for GDM diagnosis, prognosis, and severity assessment.
• These genes could also represent novel therapeutic targets for GDM management.