CPSF30和Wdr33在哺乳动物mRNA 3' 加工过程中直接与AAUAAA结合。
CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3' processing.
作者信息
Chan Serena L, Huppertz Ina, Yao Chengguo, Weng Lingjie, Moresco James J, Yates John R, Ule Jernej, Manley James L, Shi Yongsheng
机构信息
Department of Microbiology and Molecular Genetics, School of Medicine, University of California at Irvine, Irvine, California 92697, USA;
Department of Molecular Neuroscience, University College London Institute of Neurology, London WC1N 3BG, United Kingdom; Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;
出版信息
Genes Dev. 2014 Nov 1;28(21):2370-80. doi: 10.1101/gad.250993.114. Epub 2014 Oct 9.
AAUAAA is the most highly conserved motif in eukaryotic mRNA polyadenylation sites and, in mammals, is specifically recognized by the multisubunit CPSF (cleavage and polyadenylation specificity factor) complex. Despite its critical functions in mRNA 3' end formation, the molecular basis for CPSF-AAUAAA interaction remains poorly defined. The CPSF subunit CPSF160 has been implicated in AAUAAA recognition, but direct evidence has been lacking. Using in vitro and in vivo assays, we unexpectedly found that CPSF subunits CPSF30 and Wdr33 directly contact AAUAAA. Importantly, the CPSF30-RNA interaction is essential for mRNA 3' processing and is primarily mediated by its zinc fingers 2 and 3, which are specifically targeted by the influenza protein NS1A to suppress host mRNA 3' processing. Our data suggest that AAUAAA recognition in mammalian mRNA 3' processing is more complex than previously thought and involves multiple protein-RNA interactions.
AAUAAA是真核生物mRNA聚腺苷酸化位点中最保守的基序，在哺乳动物中，它被多亚基CPSF（切割和聚腺苷酸化特异性因子）复合物特异性识别。尽管它在mRNA 3'末端形成中具有关键功能，但CPSF与AAUAAA相互作用的分子基础仍不清楚。CPSF亚基CPSF160被认为与AAUAAA识别有关，但一直缺乏直接证据。通过体外和体内试验，我们意外地发现CPSF亚基CPSF30和Wdr33直接与AAUAAA接触。重要的是，CPSF30与RNA的相互作用对于mRNA 3'加工至关重要，并且主要由其锌指2和3介导，流感病毒蛋白NS1A会特异性靶向这两个锌指以抑制宿主mRNA 3'加工。我们的数据表明，哺乳动物mRNA 3'加工中AAUAAA的识别比以前认为的更为复杂，涉及多种蛋白质-RNA相互作用。
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