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Role of SNPs in the Biogenesis of Mature miRNAs.

ABSTRACT: Single nucleotide polymorphisms (SNPs) play a significant role in microRNA (miRNA) generation, processing, and function and contribute to multiple phenotypes and diseases. Therefore, whole-genome analysis of how SNPs affect miRNA maturation mechanisms is important for precision medicine. The present study established an SNP-associated pre-miRNA (SNP-pre-miRNA) database, named miRSNPBase, and constructed SNP-pre-miRNA sequences. We also identified phenotypes and disease biomarker-associated isoform miRNA (isomiR) based on miRFind, which was developed in our previous study. We identified functional SNPs and isomiRs. We analyzed the biological characteristics of functional SNPs and isomiRs and studied their distribution in different ethnic groups using whole-genome analysis. Notably, we used individuals from Great Britain (GBR) as examples and identified isomiRs and isomiR-associated SNPs (iso-SNPs). We performed sequence alignments of isomiRs and miRNA sequencing data to verify the identified isomiRs and further revealed GBR ethnographic epigenetic dominant biomarkers. The SNP-pre-miRNA database consisted of 886 pre-miRNAs and 2640 SNPs. We analyzed the effects of SNP type, SNP location, and SNP-mediated free energy change during mature miRNA biogenesis and found that these factors were closely associated to mature miRNA biogenesis. Remarkably, 158 isomiRs were verified in the miRNA sequencing data for the 18 GBR samples. Our results indicated that SNPs affected the mature miRNA processing mechanism and contributed to the production of isomiRs. This mechanism may have important significance for epigenetic changes and diseases.

SUBMITTER: Wang Y

PROVIDER: S-EPMC8233088 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Micro RNAs (miRNAs) (19-25 nucleotides in length) belong to the group of non-coding RNAs are the most abundant group of posttranscriptional regulators in multicellular organisms. They affect a gene expression by binding of fully or partially complementary sequences to the 3'-UTR of target mRNA. Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the specific pathways through which miRNAs with specific sequence or structural motifs regulate the cellular processes. In this paper we showed the broad and deep characteristics of mature miRNAs according to their sequence and structural motifs. We investigated a distinct group of miRNAs characterized by the presence of specific sequence motifs, such as UGUGU, GU-repeats and purine/pyrimidine contents. Using computational function and pathway analysis of their targeted genes, we were able to observe the relevance of sequence and the type of targeted mRNAs. As the consequence of the sequence analysis we finally provide the comprehensive description of pathways, biological processes and proteins associated with the distinct group of characterized miRNAs. Here, we found that the specific group of miRNAs with UGUGU can activate the targets associated to the interferon induction pathway or pathways prominently observed during carcinogenesis. GU-rich miRNAs are prone to regulate mostly processes in neurogenesis, whereas purine/pyrimidine rich miRNAs could be involved rather in transport and/or degradation of RNAs. Additionally, we have also analyzed the simple sequence repeats (SSRs). Their variation within mature miRNAs might be critical for normal miRNA regular activity. Expansion or contraction of SSRs in mature miRNA might directly affect its mRNA interaction or even change the function of that distinct miRNA. Our results prove that due to the specific sequence features, these molecules can also be involved in well-defined cellular processes depending on their sequence contents. The pathway mapping and theoretical gene target identification allowed us to create a biological framework to show the relevance of the specific miRNAs in regulation the distinct type of targets.

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Role of SNPs in the Biogenesis of Mature miRNAs.

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