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寻找匹配物:序列特异性 RNA 结合蛋白的结构、功能与应用。

Searching for a Match: Structure, Function and Application of Sequence-Specific RNA-Binding Proteins.

机构信息

University of California-Riverside, Riverside, CA, USA.

出版信息

Plant Cell Physiol. 2019 Sep 1;60(9):1927-1938. doi: 10.1093/pcp/pcz072.

DOI:10.1093/pcp/pcz072
PMID:31329953
Abstract

Plants encode over 1800 RNA-binding proteins (RBPs) that modulate a myriad of steps in gene regulation from chromatin organization to translation, yet only a small number of these proteins and their target transcripts have been functionally characterized. Two classes of eukaryotic RBPs, pentatricopeptide repeat (PPR) and pumilio/fem-3 binding factors (PUF), recognize and bind to specific sequential RNA sequences through protein-RNA interactions. These modular proteins possess helical structural units containing key residues with high affinity for specific nucleotides, whose sequential order determines binding to a specific target RNA sequence. PPR proteins are nucleus-encoded, but largely regulate post-transcriptional gene regulation within plastids and mitochondria, including splicing, translation and RNA editing. Plant PUFs are involved in gene regulatory processes within the cell nucleus and cytoplasm. The modular structures of PPRs and PUFs that determine sequence specificity has facilitated identification of their RNA targets and biological functions. The protein-based RNA-targeting of PPRs and PUFs contrasts to the prokaryotic cluster regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas) that target RNAs in prokaryotes. Together the PPR, PUF and CRISPR-Cas systems provide varied opportunities for RNA-targeted engineering applications.

摘要

植物编码了超过 1800 种 RNA 结合蛋白(RBPs),这些蛋白在基因调控的各个环节发挥作用,从染色质组织到翻译,然而,只有少数这些蛋白及其靶转录本的功能得到了充分的研究。两类真核 RBPs,五肽重复(PPR)和 pumilio/fem-3 结合因子(PUF),通过蛋白-RNA 相互作用识别和结合特定的连续 RNA 序列。这些模块化的蛋白具有螺旋结构单元,其中包含与特定核苷酸具有高亲和力的关键残基,其顺序决定了与特定靶 RNA 序列的结合。PPR 蛋白是核编码的,但主要在质体和线粒体中调节转录后基因调控,包括剪接、翻译和 RNA 编辑。植物 PUFs 参与细胞核和细胞质中的基因调控过程。PPR 和 PUF 的模块化结构决定了序列特异性,这有助于鉴定它们的 RNA 靶标和生物学功能。PPR 和 PUF 的基于蛋白的 RNA 靶向与原核的规律成簇间隔短回文重复(CRISPR)相关蛋白(Cas)形成对比,后者在原核生物中靶向 RNA。PPR、PUF 和 CRISPR-Cas 系统一起为 RNA 靶向工程应用提供了多样化的机会。

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