Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genetic regulation of human isomiR biogenesis

Version 1 : Received: 17 July 2023 / Approved: 18 July 2023 / Online: 18 July 2023 (07:52:22 CEST)

A peer-reviewed article of this Preprint also exists.

Jiang, G.; Reiter, J.L.; Dong, C.; Wang, Y.; Fang, F.; Jiang, Z.; Liu, Y. Genetic Regulation of Human isomiR Biogenesis. Cancers 2023, 15, 4411. Jiang, G.; Reiter, J.L.; Dong, C.; Wang, Y.; Fang, F.; Jiang, Z.; Liu, Y. Genetic Regulation of Human isomiR Biogenesis. Cancers 2023, 15, 4411.

Abstract

MicroRNA plays 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 5’-extension of hsa-miR-423-3p and 5’-trimming of hsa-miR-423-5p. Comparison of breast cancer and normal samples revealed that 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 microRNA.

Keywords

microRNA; isomiR; genetic association

Subject

Computer Science and Mathematics, Mathematical and Computational Biology

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