《生命科学》 2026, 38(10): 1830-1844

核苷酸修饰对microRNA生物合成和功能的影响

刘涛^1,* , 付楠楠² , 刘蕊^1,*

¹天津市第一中心医院（南开大学附属第一中心医院），国家卫生健康委员会危重病急救医学重点实验室，天津 300192 ²天津市儿童医院（天津大学儿童医院）消化科，天津 300134

摘　要：

微小RNA（microRNA， miRNA）是一类细胞内源性的小分子非编码RNA家族，在转录后水平广泛调控基因表达。在真核细胞miRNA生成初级转录本、加工成为前体，直至最终成为功能性成熟体的各个阶段，都存在核苷酸修饰，即在经典的4 种核糖核苷酸的基础上，通过酶促反应生成其他类型核苷酸，或不依赖模板在RNA末端额外添加核苷酸。本文综述了miRNA生物合成过程中常见的核苷酸修饰类型，包括甲基化、末端加尾、核苷酸编辑、氧化、磷酸化等修饰。核苷酸修饰可能影响不同阶段miRNA的稳定性、加工成熟活性，miRNA成熟体的核苷酸修饰也能够影响其靶基因识别谱，或改变其对靶基因的抑制强度。miRNA的核苷酸修饰与细胞的多种生理和病理过程密切相关，并且可作为临床疾病诊断的分子标志或治疗靶点，具有广阔的临床应用前景。

通讯作者：刘涛 , Email:liutao@nankai.edu.cn 刘蕊 , Email:liurui20210905@163.com

Effects of nucleotide modification on microRNA biogenesis and function

LIU Tao^1,* , FU Nan-Nan² , LIU Rui^1,*

¹National Health Commission’s Key Laboratory of Critical Care Medicine, Tianjin First Central Hospital (First Central Affiliated Hospital of Nankai University), Tianjin 300192, China ²Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin 300134, China

Abstract:

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs (ncRNAs) that widely regulate gene expression at the posttranscriptional level. In eukaryotic cells, miRNAs are initially transcribed to form primary transcripts, which are subsequently processed into precursors, and finally mature into functional miRNAs. Throughout these stages, miRNAs may undergo nucleotide modifications, which refer to enzymatic processes that generate non-canonical nucleotides from the four standard types of ribonucleotides, or append additional nucleotides to the ends of miRNAs in a template-independent manner. This review summarizes the common nucleotide modifications occurring during miRNA biogenesis, including methylation, terminal tailing, nucleotide editing, oxidation, and phosphorylation. On the one hand, certain types of nucleotide modifications enhance miRNA functions by promoting miRNA biogenesis, increasing the stability of miRNA molecules during the processing stages, or facilitating the binding of miRNAs to their target RNAs. On the other hand, some nucleotide modifications exert inhibitory effects on miRNA functions, manifested in suppression of miRNA biogenesis, induction of miRNA degradation, or inhibition of the interaction between mature miRNAs and their targets. In addition, specific nucleotide modifications occurring in mature miRNAs can also alter the target RNA profile of miRNAs. Nucleotide modifications of miRNAs possess certain clinical application value. First, the types and levels of miRNA nucleotide modifications can serve as molecular biomarkers for disease diagnosis, prognostic evaluation, and drug efficacy assessment. Second, artificial modulation of the extent of miRNA nucleotide modifications can alter their regulatory capacity toward targeted disease-associated genes, thereby exerting therapeutic effects on certain diseases. Third, when miRNAs are used as oligonucleotide therapeutics, the introduction of specific nucleotide modifications may enhance drug potency. Nevertheless, the short sequence length and large number of miRNA family members pose considerable challenges to applications related to nucleotide modifications. Researchers need to optimize the procedures for their clinical applications in the future.

Communication Author：LIU Tao , Email:liutao@nankai.edu.cn LIU Rui , Email:liurui20210905@163.com