Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
J Biol Chem. 2011 Jun 10;286(23):20152-62. doi: 10.1074/jbc.M110.139261. Epub 2011 Apr 5.
CCCH zinc finger proteins (ZC3Hs) are a novel class of RNA-binding protein involved in post-transcriptional mechanisms controlling gene expression. We show TbZC3H20 from Trypanosoma brucei, the causative agent of sleeping sickness and other diseases, stabilizes two developmentally regulated transcripts encoding a mitochondrial carrier protein (MCP12) and trans-sialidase (TS-like E). TbZC3H20 is shown to be an RNA-binding protein that is enriched in insect procyclic form T. brucei and is the first ZC3H discovered controlling gene expression through modulating mRNA abundance in trypanosomes. Previous studies have demonstrated that RNA recognition motif-containing and PUF family RNA-binding proteins can control gene expression by stabilizing specific target mRNA levels. This work is the first to describe a ZC3H stabilizing rather than destabilizing target mRNAs as a regulatory mechanism and the first report of a ZC3H regulating a gene encoding a mitochondrial protein. This suggests a broader role for ZC3Hs in post-transcriptional regulation of gene expression than previously thought.
CCCH 锌指蛋白 (ZC3Hs) 是一类新的 RNA 结合蛋白,参与转录后机制调控基因表达。我们展示了来自引起昏睡病和其他疾病的布氏锥虫的 TbZC3H20,稳定了两个发育调控的转录本,编码一个线粒体载体蛋白 (MCP12) 和转唾液酸酶 (TS-like E)。TbZC3H20 被证明是一种 RNA 结合蛋白,在昆虫前鞭毛体形式的 T. brucei 中富集,是第一个通过调节锥虫中 mRNA 丰度来控制基因表达的 ZC3H。先前的研究表明,含有 RNA 识别模体和 PUF 家族 RNA 结合蛋白可以通过稳定特定的靶 mRNA 水平来控制基因表达。这项工作首次描述了 ZC3H 通过稳定而不是破坏靶 mRNA 作为一种调节机制,以及首次报道 ZC3H 调节编码线粒体蛋白的基因。这表明 ZC3H 在基因表达的转录后调控中发挥了比以前认为的更广泛的作用。