Genetic Regulation of Human IsomiR Biogenesis

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Sep 9

PMID 37686687

Authors

Guanglong Jiang

Jill L Reiter

Chuanpeng Dong

Yue Wang

Fang Fang

Zhaoyang Jiang

Yunlong Liu

Affiliations

Soon will be listed here.

Abstract

MicroRNAs play a critical role in regulating gene expression post-transcriptionally. Variations in mature microRNA sequences, known as isomiRs, arise from imprecise cleavage and nucleotide substitution or addition. These isomiRs can target different mRNAs or compete with their canonical counterparts, thereby expanding the scope of miRNA post-transcriptional regulation. Our study investigated the relationship between cis-acting single-nucleotide polymorphisms (SNPs) in precursor miRNA regions and isomiR composition, represented by the ratio of a specific 5'-isomiR subtype to all isomiRs identified for a particular mature miRNA. Significant associations between 95 SNP-isomiR pairs were identified. Of note, rs6505162 was significantly associated with both the 5'-extension of hsa-miR-423-3p and the 5'-trimming of hsa-miR-423-5p. Comparison of breast cancer and normal samples revealed that the expression of both isomiRs was significantly higher in tumors than in normal tissues. This study sheds light on the genetic regulation of isomiR maturation and advances our understanding of post-transcriptional regulation by microRNAs.

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