King Valeria M, Borchert Glen M
Department of Biology, University of South Alabama, Mobile, AL, 36688, USA.
Department of Pharmacology, University of South Alabama, Mobile, AL, 36688, USA.
Methods Mol Biol. 2017;1617:27-37. doi: 10.1007/978-1-4939-7046-9_2.
MiRNAs are ~20 nt small RNAs that regulate networks of proteins using a seed region of nucleotides 2-8 to complement the 3' UTR of target mRNAs. The biogenesis and function of miRNAs as translational repressors is facilitated by protein counterparts that process primary and precursor miRNAs to maturity (Drosha/DCGR8 and Dicer/TRBP respectively) and incorporate miRNAs into the protein complex RISC to recognize and repress target mRNAs (RISC proteins: Ago/TRBP1/TRBP2/DICER). Similarly, siRNAs through comparable mechanisms are loaded into the protein complex RITS to heterochromatin formation of DNA and suppress transcription of particular genes. MiRNAs are also regulated themselves through many different pathways including transcriptional regulation, post-transcriptional RNA editing, and RNA tailing. Dysregulation of miRNAs and the protein participants that mature them are implicated in the development of a number of diseases, tumorigenesis, and arrested development of embryonic cells. In this chapter, we will explore the biosynthesis, function, and regulation of miRNAs.
微小RNA(miRNA)是约20个核苷酸的小RNA,其利用核苷酸2 - 8的种子区域来调控蛋白质网络,以互补靶标信使核糖核酸(mRNA)的3'非翻译区(UTR)。作为翻译抑制因子的miRNA的生物合成和功能,由将初级和前体miRNA加工成熟的相应蛋白质(分别为Drosha/DCGR8和Dicer/TRBP)促进,并将miRNA整合到蛋白质复合物RNA诱导沉默复合体(RISC)中以识别和抑制靶标mRNA(RISC蛋白:AGO/TRBP1/TRBP2/DICER)。同样,小干扰RNA(siRNA)通过类似机制被加载到蛋白质复合物RNA诱导转录沉默复合体(RITS)中,以形成DNA异染色质并抑制特定基因的转录。miRNA自身也通过许多不同途径受到调控,包括转录调控、转录后RNA编辑和RNA加尾。miRNA及其成熟过程中的蛋白质参与者的失调与多种疾病的发展、肿瘤发生以及胚胎细胞发育停滞有关。在本章中,我们将探讨miRNA的生物合成、功能和调控。