MicroRNAs (miRNAs) are a family of endogenous small noncoding RNAs involved in various developmental and physiological
processes by negatively regulating gene expression [Bartel 2004;
Zhang et al., 2007]. To date, thousands of miRNAs in human and
other species have been identified in miRBase database [Kozomara
and Griffiths-Jones, 2011]. miRNA genes may reside in introns of
protein coding genes or intergenic regions. They are initially transcribed in the nucleus as long primary transcripts (pri-miRNAs)
and further processed by the RNase Drosha to hairpin precursor
miRNAs (pre-miRNAs) [Lee et al., 2003]. Then, the pre-miRNA
hairpins are exported to the cytoplasm and processed into ∼22 nt
miRNA duplex by RNase Dicer [Bartel, 2004]. One strand from
the miRNA duplex (miR-5p/miR-3p duplex) containing the less
stable 5 end is preferentially selected and loaded onto the RNAinduced silencing complex (RISC) to produce a functional, mature
miRNA (MIR) [Khvorova et al., 2003]. MIRs recognize their target mRNAs mainly by base-pairing interaction between nucleotides
2 and 8 (seed region) from its 5 end and the complementary nucleotides on the 3 untranslated region (3
UTR) of target mRNAs
[Lai, 2002; Lewis et al., 2003]. Currently, it is estimated that an
miRNA may regulate hundreds of target genes and most of human
protein coding genes are regulated by miRNAs [Betel et al., 2008;
Friedman et al., 2009; Krek et al., 2005].
Single nucleotide polymorphisms (SNPs) are important variations for the diversity among individuals, as well as leading to phenotypes, traits, and diseases [Shastry, 2009]. Since miRNAs are wide
and key regulators of gene expression, miRNA-related SNPs including SNPs in miRNA genes and target sites may function as regulatory
SNPs through modifying miRNA regulation to affect the phenotypes and disease susceptibility [Ryan et al., 2010]. Moreover, SNPs
located in MIRs are likely to cause complex influence by affecting
MIR maturation, functional strand selection, and target selection.
To date, a number of studies have demonstrated that SNPs in target
sites or miRNA genes are associated with diseases [Jazdzewski et al.,
2008; Mencia et al., 2009; Ryan et al., 2010; Saunders et al., 2007;
Sethupathy and Collins, 2008; Sun et al., 2009]. For example, an SNP
MicroRNAs (miRNAs) are a family of endogenous small noncoding RNAs involved in various developmental and physiologicalprocesses by negatively regulating gene expression [Bartel 2004;Zhang et al., 2007]. To date, thousands of miRNAs in human andother species have been identified in miRBase database [Kozomaraand Griffiths-Jones, 2011]. miRNA genes may reside in introns ofprotein coding genes or intergenic regions. They are initially transcribed in the nucleus as long primary transcripts (pri-miRNAs)and further processed by the RNase Drosha to hairpin precursormiRNAs (pre-miRNAs) [Lee et al., 2003]. Then, the pre-miRNAhairpins are exported to the cytoplasm and processed into ∼22 ntmiRNA duplex by RNase Dicer [Bartel, 2004]. One strand fromthe miRNA duplex (miR-5p/miR-3p duplex) containing the lessstable 5 end is preferentially selected and loaded onto the RNAinduced silencing complex (RISC) to produce a functional, maturemiRNA (MIR) [Khvorova et al., 2003]. MIRs recognize their target mRNAs mainly by base-pairing interaction between nucleotides2 and 8 (seed region) from its 5 end and the complementary nucleotides on the 3 untranslated region (3UTR) of target mRNAs[Lai, 2002; Lewis et al., 2003]. Currently, it is estimated that anmiRNA may regulate hundreds of target genes and most of humanprotein coding genes are regulated by miRNAs [Betel et al., 2008;Friedman et al., 2009; Krek et al., 2005].Single nucleotide polymorphisms (SNPs) are important variations for the diversity among individuals, as well as leading to phenotypes, traits, and diseases [Shastry, 2009]. Since miRNAs are wideand key regulators of gene expression, miRNA-related SNPs including SNPs in miRNA genes and target sites may function as regulatorySNPs through modifying miRNA regulation to affect the phenotypes and disease susceptibility [Ryan et al., 2010]. Moreover, SNPslocated in MIRs are likely to cause complex influence by affectingMIR maturation, functional strand selection, and target selection.To date, a number of studies have demonstrated that SNPs in targetsites or miRNA genes are associated with diseases [Jazdzewski et al.,2008; Mencia et al., 2009; Ryan et al., 2010; Saunders et al., 2007;Sethupathy and Collins, 2008; Sun et al., 2009]. For example, an SNP
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