miRNAs are small non-coding regulators of gene expression that are estimated to regulate over 60% of all human genes. Each miRNA can target multiple mRNA targets and as such, miRNAs are responsible for some of the ‘fine tuning’ of gene expression and are implicated in regulation of all cellular processes. miRNAs bind to target genes by sequence complementarity, resulting in target degradation or translational blocking and usually a reduction in target gene expression. Like mRNA, miRNAs are transcribed from genomic DNA and are processed in several steps that are heavily reliant on correct secondary and tertiary structure. Secondary structure is determined by RNA sequence, which is in turn determined by the sequence of the genome. The human genome, however, like most eukaryotes is variable. Large numbers of SNPs (single nucleotide polymorphisms), small insertions and deletions (indels) and CNVs (copy number variants) have been described in our genome. Should this genetic variation occur in regions critical for the correct secondary structure or target binding, it may interfere with normal gene regulation and cause disease. In this review, we outline the consequences of genetic variation involving different aspects of miRNA biosynthesis, processing and regulation, with selected examples of incidences when this has potential to affect human disease.

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