Abstract
BackgroundThe HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3′ regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3′ region of HTR1B.ResultsWe found that the haplotype, A-G-Del-C-T-Ins-A, enhanced the expression level compared to the main haplotype; A-G-Del-C-G-Ins-A; G-G-Del-C-G-Ins-G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that + 2440 ~ + 2769 bp and + 1953 ~ + 2311 bp regions both had negative effects on gene expression.ConclusionsThe 3′ region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3′ region includes several effector binding sites that induce an inhibitory effect on gene expression.
Highlights
The hydroxytryptamine receptor 1B gene (HTR1B) gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders
We investigated the effects of several haplotypes of the HTR1B gene, and truncated fragments of the 3′ region of HTR1B, on reporter gene expression in order to analyze the function of the 3′ region
The regulatory effects of polymorphisms of the 3′ region of HTR1B Haplotype recombinants were transfected into SK-N-SH, HEK-293, and U87 cell lines
Summary
The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation plays a important role in gene expression [1], including in the function of the 3′ regulatory region on mRNA. The miRNA regulatory effects are closely related to variations such as polymorphisms or mutations, which are located at miRNA target gene binding sequences. Single nucleotide polymorphisms (SNP) in miRNA target sites are known as polymiRTS, which may produce many functional consequences. They may generate a new miRNA target site or destroy an existing one, or change miRNA–mRNA binding efficiency [8]. A review by Sethupathy et al emphasized the opinion that poly-miRTS is disease related [8]
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