脊椎动物Argonaute蛋白的研究进展

Research progress in Argonaute proteins of vertebrates

摘要:

Argonaute蛋白是广泛活跃于不同生物的整个生命周期、与小RNA (small RNA, sRNA)结合并调控基因表达的一类蛋白。脊椎动物Argonaute蛋白有2个分支，Ago蛋白和Piwi蛋白，均包含N、L1、L2、PAZ、MID和PIWI结构域。N结构域有助于sRNA单链加载；L1、L2起结构域连接作用；PAZ和MID结构域通过锚定sRNA发挥功能；部分Argonaute蛋白的PIWI结构域类似RNase H，具有核酸内切酶功能。Ago蛋白主要在转录及转录后水平调控基因表达；Piwi蛋白主要存在于生殖细胞，通过多种途径沉默转座子以保护机体基因组免受破坏，同时参与基因表达调控。本文结合近年来Argonaute蛋白在晶体结构、功能解析、表达模式等方面的研究进展，从蛋白结构、sRNA依赖性、基因表达调控机制、生物学功能等方面对脊椎动物Ago和Piwi蛋白分支进行比较阐述，以期阐明其在表观遗传调控中的作用，并为后续Argonaute蛋白的深入研究和实际应用提供参考。

Abstract:

Argonaute proteins are active throughout the lifetime in a variety of organisms and they bind to small RNAs (sRNAs) to regulate gene expression. The Argonaute proteins of vertebrates can be classified into two clades: the Ago clade and the Piwi clade. Both clades have N, L1, L2, PAZ, MID and PIWI domains. The N domain is involved in the loading of sRNAs. L1 and L2 domains facilitate the linking between domains. The PAZ and MID domains exert functions by anchoring sRNAs. The PIWI domain of some Argonaute proteins has RNase H-like structure and exerts the endonuclease function. Ago proteins regulate gene expression at transcriptional and post-transcriptional levels. Piwi proteins mainly exist in the germ cells, silencing transposons in different ways to keep genome integrality and regulating gene expression. In recent years, great progress has been made in Argonaute proteins in terms of the crystal structures, functions, and expression patterns. By reviewing the relevant studies, we elaborate on the structures, sRNA dependence, gene expression regulation, and biological roles of the Ago and Piwi proteins in vertebrates, aiming to clarify the roles of Argonaute proteins in epigenetic regulation and provide a reference for further research and application of these proteins.