Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that are involved in translational regulation of the messenger RNA molecules. Sequence variations in the genes encoding miRNAs could influence their biogenesis and function. MiR-15b plays an important role in cellular proliferation, apoptosis and the cell cycle. Here, we report the identification of a C58T mutation in porcine pre-miR-15b. Through in vitro and in vivo experiments, we determined that this mutation blocks the transition from pri-miRNA to pre-miRNA, alters the strand selection between miR-15b-5p and miR-15b-3p, and obstructs biogenesis of the downstream miR-16-1. These results serve to highlight the importance of miRNA mutations and their impacts on miRNA biogenesis.
Highlights
MicroRNAs are endogenous non-coding RNAs, ~22 nt in length, that function as negative regulators of gene expression at the post-transcriptional level [1,2,3], exerting pervasive regulatory impact on most biological processes [2,4,5]
The mechanisms that control miRNA biogenesis are precisely regulated, from both spatial and temporal perspectives; such dynamic regulation is necessary to control the myriad targeting of miRNAs to the multitudes of genes that they act upon to finely modulate expression [31]
We found that rs334680106 blocks the processing of pri-miRNA to premiRNA and alters the expression level of miR-15b and influences the strand selection of miR-15b; the significant genetic effect of rs334680106 was confirmed in blood specimens taken from living animals
Summary
MicroRNAs (miRNAs) are endogenous non-coding RNAs, ~22 nt in length, that function as negative regulators of gene expression at the post-transcriptional level [1,2,3], exerting pervasive regulatory impact on most biological processes [2,4,5]. The pri-miRNAs are cleaved by the Microprocessor complex of two RNase III enzymes—Drosha and DGCR8 —to liberate hairpin-shaped precursor transcripts (pre-miRNAs) [7,8].
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