微小RNA在转录后调节基因表达中发挥关键作用。成熟微小RNA序列的变异，即isomiRs，来源于不精确的切割以及核苷酸的置换或加入。这些isomiRs能够靶向不同的mRNA或与它们的规范对应物竞争，从而扩大了miRNA转录后调节的范围。我们的研究调查了前体miRNA区域的顺式作用单核苷酸多态性（SNPs）与isomiR组成之间的关系，通过特定5'-isomiR亚型与为特定成熟miRNA鉴定的所有isomiRs的比率来表示。已确定了95个SNP-isomiR对之间的显著关联。值得注意的是，rs6505162与hsa-miR-423-3p的5'-延长和hsa-miR-423-5p的5'-修剪均有显著关联。对比乳腺癌和正常样本发现，这两个isomiR在肿瘤中的表达显著高于正常组织。该研究揭示了isomiR成熟的遗传调控，提升了我们对微小RNA转录后调节的认识。

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.