Alternative Polyadenylation Results in mRNA Transcript Instability in Gestational Diabetes Mellitus

To study the characteristics of selective polyadenylation (APA) in gestational diabetes mellitus (GDM) by poly(A) site sequencing and to explore the role of APA process in the pathogenesis of GDM.

Three pregnant women diagnosed as GDM in our hospital were randomly selected as the GDM group, and three healthy pregnant women at the same time as the control group. The placental tissues of two groups of pregnant women after delivery were collected for high-throughput transcriptome sequencing (RNA-seq) and poly(A) site sequencing (PAS-seq) to screen differentially expressed genes and variable 3'UTR genes in GDM. Gene Ontology (GO) analysis and pathway analysis were used to analyze the functional classification and pathway of differential genes, and preliminarily explore the susceptible genes in GDM.

Compared with the control group, there were 202 TTS loci in the GDM group, including 103 genes with shortened TTS loci and 99 genes with delayed TTS loci. There were 57 genes with significant difference in TTS (P<0.05). Subsequently, we found that VCPIP1 and LGR4 were differentially expressed in RNA-seq. The genes in advance of TTS locus were enriched in biological processes such as cell development, protein transport and phosphorylation, signal transduction, etc. Delayed TTS genes are enriched in biological processes such as transcriptional regulation, cell migration and cycle, DNA repair and damage.

The abnormality of APA process may be involved in the occurrence and development of GDM. The genes with significantly different changes in TTS locus may become biomarkers or predictors for GDM to assess the incidence, disease progression and disease severity, and may also become potential targets for GDM treatment.