Association of miR-938G>A Polymorphisms with Primary Ovarian Insufficiency (POI)-Related Gene Expression.

Sung Cho,Ji Kim,Young Kim,Hui An,Woo Lee,Jung Ko,Nam Kim,Eun Ahn

doi:10.3390/ijms18061255

Abstract

MicroRNAs (miRNAs) post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to investigate whether polymorphisms in miR-938 are associated with the risk of primary ovarian insufficiency (POI) and POI-related target gene regulation. We identified the miR-938G>A polymorphisms within the seed sequence of mature miRNA and aligned the seed sequence with the 3′ untranslated region (UTR) of the gonadotropin-releasing hormone receptor (GnRHR) mRNA, a miR-938 target gene. We found that the binding of miR-938 to the 3′-UTR of GnRHR mRNA was significantly different between normal and variant alleles. Our data suggests that the dysregulation of miR-938G>A influences the binding to GnRHR and that miR-938G>A polymorphisms might contribute to regulation of POI-related target genes.

Highlights

MicroRNAs are small, noncoding, single-stranded RNA molecules that form base pairs with target messenger RNA [1]
Previous reports show that miRNAs modulate gene expression by targeting messenger RNA (mRNA) for deregulation or translational repression [2]. miRNAs are typically composed of about 23 nucleotides and regulate target genes through RNA silencing and post-transcriptional regulation of gene expression [3]. miRNAs have been implicated in the regulation of several biochemical pathways in many eukaryotic organisms [4,5]. miRNAs are transcribed into long precursor transcripts called primary-miRNAs by RNA polymerase II, and the pri-miRNAs are converted to pre-miRNAs by DROSHA, an enzyme that belongs to an RNase type III family in a complex with DiGeorge Syndrome Critical Region 8 (DGCR8) [6,7]
RNA-induced silencing complex (RISC) is responsible for the gene silencing mediated by miRNA expression and RNA interference (RNAi). miRNAs carry out their biological functions by binding to the 3 -untranslated region (UTR) of target mRNAs, thereby repressing expression

Summary

Introduction

MicroRNAs (miRNAs) are small, noncoding, single-stranded RNA molecules that form base pairs with target messenger RNA (mRNA) [1]. Previous reports show that miRNAs modulate gene expression by targeting mRNA for deregulation or translational repression [2]. MiRNAs are typically composed of about 23 nucleotides and regulate target genes through RNA silencing and post-transcriptional regulation of gene expression [3]. The pre-miRNA is exported to the cytoplasm by the exportin (Exp5)–ras-related nuclear protein (RAN)-Guanosine-5 -triphosphate (GTP) complex [8]. The Ran GTPase binds Exp and forms a nuclear heterotrimer with pre-miRNA [9]. RISC is responsible for the gene silencing mediated by miRNA expression and RNA interference (RNAi). MiRNAs carry out their biological functions by binding to the 3 -untranslated region (UTR) of target mRNAs, thereby repressing expression. A single miRNA may regulate multiple targets and act as a master controller of gene expression

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