Background
SNPs within pre-miRNA regions play a significant role in miRNA generation, processing and function by different molecular mechanisms and are thought to be major contributors to the variations in phenotypes and diseases. Therefore, whole-genome analysis of how SNPs affect mature miRNA biogenesis is important for precision medicine.
Results
In this study, aiming to analyze the role of SNPs in mature miRNA biogenesis genome-wide, we constructed a SNP-pre-miRNA database, named miRSNPBase, consisting of 886 pre-miRNAs and 2640 SNPs based on the latest data. Then, we identified 10574 SNP-pre-miRNAs based on 886 pre-miRNAs and their associated 2640 SNPs, and we performed genome-wide association analyses to identify isoform miRNAs (isomiRs) based on miRFind that are associated with the mechanism of SNPs affecting miRNA maturation. A total of 4235 nor-SNP-pre-miRNAs based on 480 nor-pre-miRNAs and 1250 nor-SNPs were identified. We analyzed the effects of SNP type, SNP location and SNP-mediated free energy change during mature miRNA biogenesis and found that they are closely related to mature miRNA biogenesis. In addition, the MAF distribution of the iso-pre-miRNAs and nor-SNPs was analyzed based on the 1000 Genomes Project. The results demonstrated that individuals who contained the iso-SNPs were in the minority, and those who contained the nor-SNPs were in the majority. Notably, to verify our method and identify important biomarkers, we identified isomiRs and iso-SNPs in 18 GBR individuals of European origin. In the results, 209 iso-pre-miRNA candidates and 71 verified iso-pre-miRNAs of the 18 GBR samples were identified, and 2667 isomiRs of 209 pre-miRNAs were verified by miRNA sequencing data.
Conclusions
Our results clearly indicated that SNPs that altered the mature miRNA splicing mechanism and led to the production of isomiRs, were closely related to and affected normal life processes, and led to epigenetic changes and diseases.