The Biogenesis, Regulation, and Canonical and Noncanonical Functional Machinery of miRNAs
摘要
MicroRNAs (miRNAs) are small noncoding RNAs that play a central role in posttranscriptional gene regulation across eukaryotes. This book chapter explores the biogenesis, regulatory mechanisms, and both canonical and noncanonical functions of miRNAs. The biogenesis of miRNAs involves sequential processing by the Drosha-DGCR8 complex and Dicer, followed by incorporation into Argonaute (AGO)-containing RNA-induced silencing complexes (RISCs). Precise strand selection and guide strand retention are mediated by thermodynamic asymmetry, RNA-binding proteins, and ATP-dependent helicases. AGO proteins facilitate target mRNA silencing via cleavage or translational repression, driven by the seed sequence of the miRNA. Beyond their classical role in gene silencing, miRNAs are also implicated in chromatin modification, immune responses, and alternative splicing. Regulation of miRNA function occurs at multiple levels, including RNA editing, 3′ ends tailing, and turnover by exonucleases such as Eri1 and SDNs. Posttranslational modifications of AGO proteins further influence RISC activity, localization, and stability. Feedback loops between miRNA availability and AGO abundance maintain homeostasis within the silencing machinery. This chapter underscores the complexity and versatility of miRNA-mediated pathways and highlights their relevance in development, epigenetic inheritance, stress responses, and disease. Understanding the integrated regulation and multifaceted roles of miRNAs provides new insights into gene regulatory networks and therapeutic opportunities.