Significance of Single-Nucleotide Variants in Long Intergenic Non-protein Coding RNAs

Abstract

Single-nucleotide variants (SNVs) are the most common genetic variants and universally present in the human genome. Genome-wide association studies (GWASs) have identified a great number of disease or trait-associated variants, many of which are located in non-coding regions. Long intergenic non-protein coding RNAs (lincRNAs) are the major subtype of long non-coding RNAs; lincRNAs play crucial roles in various disorders and cellular models via multiple mechanisms. With rapid growth in the number of the identified lincRNAs and genetic variants, there is great demand for an investigation of SNVs in lincRNAs. Hence, in this article, we mainly summarize the significant role of SNVs within human lincRNA regions. Some pivotal variants may serve as risk factors for the development of various disorders, especially cancer. They may also act as important regulatory signatures involved in the modulation of lincRNAs in a tissue- or disorder-specific manner. An increasing number of researches indicate that lincRNA variants would potentially provide additional options for genetic testing and disease risk assessment in the personalized medicine era.

Keywords: biological function; disease susceptibility; long/large intergenic non-protein coding RNA; single-nucleotide variant; transcription.

FIGURE 1

(A) Genomic distribution of single-nucleotide variants in cancers; a majority of cancer-associated single-nucleotide variants (SNVs) [single-nucleotide polymorphisms (SNPs)] are found in the intergenic or intronic regions, and only small numbers are located in protein-coding regions of the human genome. (B) Classification of long non-coding RNA (lncRNA) transcripts; long intergenic non-protein coding RNA (lincRNA) is a major subtype of lncRNA.

FIGURE 2

Graphical representations of the driving effect of variants [single-nucleotide variants (SNVs)] on long intergenic non-protein coding RNA (lincRNA) regions. (A) Genetic variants located in promoter may affect the binding of transcription factors and regulate the transcription of lincRNAs. (B) Genetic variants on enhancer affect the binding of transcription co-regulators and regulate lincRNA expression. (C) Genetic variants on intron may affect the process of splicing and stability of lincRNA conformation. (D) Genetic variants located in exons affect the lincRNA secondary structure, lincRNA stability, and interactive function. (E) Genetic variants on exons may affect the sponging of microRNAs (miRNAs).