Abstract
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that repress their targets at post transcriptional level. Single Nucleotide Polymorphisms (SNPs) in miRNAs can lead to severe defects to the functions of miRNAs and might result in diseases. Although several studies have tried to identify the SNPs in human miRNA genes or only in the mature miRNAs, there are only limited endeavors to explain the distribution of SNPs in these important genes. After a genome-wide scan for SNPs in human miRNAs, we totally identified 1899 SNPs in 961 out of the 1527 reported miRNA precursors of human, which is the most complete list of SNPs in human miRNAs to date. More importantly, to explain the distributions of SNPs existed in human miRNAs, we comprehensively and systematically analyzed the identified SNPs in miRNAs from several aspects. Our results suggest that conservation, genomic context, secondary structure, and functional importance of human miRNAs affect the accumulations of SNPs in these genes. Our results also show that the number of SNPs with significantly different frequencies among various populations in the HapMap and 1000 Genome Project data are consistent with the geographical distributions of these populations. These analyses provide a better insight of SNPs in human miRNAs and the spreading of the SNPs in miRNAs in different populations.
Highlights
MicroRNAs are endogenous small non-coding RNAs that control the translation and stability of mRNAs at transcriptional level [1]
These studies only listed the frequencies of Single Nucleotide Polymorphisms (SNPs) in miRNA genes based on the HapMap and 1000 Genomes Project data without analyzing them deeply and no systematical endeavors were dedicated to the explanation of the distribution of SNPs in human miRNAs except [22]
Our results show that (1) conserved miRNAs tend to have lower average SNP densities; (2) clustered miRNAs tend to have lower SNP densities than individual ones; (3) miRNAs with at least two SNPs are enriched in fragile sites; (4) different substitutions of the SNPs in miRNAs have different frequencies which is attributed to their contributions to the stabilities of the secondary structure of pre-miRNAs; and (5) miRNAs frequently associated with diseases tend to have less SNPs
Summary
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that control the translation and stability of mRNAs at transcriptional level [1]. MiRNAs are initially transcribed in the nucleus as long primary transcripts (pri-miRNAs) and further processed by the RNase III Drosha to miRNA precursors with typical hairpin structure [2]. The pre-miRNAs are exported to the cytoplasm by exportin 5 [3] and processed into about 21 nt miRNA duplexes by RNase Dicer [4]. One strand from the miRNA duplex is preferentially selected and loaded onto the RNA-Induced Silencing Complex (RISC) to produce a functional mature miRNA [5]. Mature miRNA recognizes its target mRNAs mainly by base-pairing between the second to eighth nucleotides (seed region) from its 59 end and the complementary nucleotides on the 39 untranslated region (39 UTR) of target mRNAs [6]. It is estimated that the expression of about one-third of all proteincoding genes are regulated by miRNAs [10]
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