CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3' processing.
CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3' processing.
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DOI：
10.1101/gad.250993.114
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发表时间：
2014-11-01
影响因子：
10.5
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Chan SL;Huppertz I;Yao C;Weng L;Moresco JJ;Yates JR 3rd;Ule J;Manley JL;Shi Y
AAUAAA是真核生物mRNA多聚腺苷酸化位点中最高度保守的基序，在哺乳动物中，被多亚基CPSF复合物特异性识别。Chan等人发现CPSF亚基CPSF 30和Wdr 33直接接触AAUAAA。CPSF 30-RNA相互作用对于mRNA 3′加工是必需的，并且主要由其锌指2和3介导，其被流感蛋白NS 1A特异性靶向以抑制宿主mRNA 3′加工。AAUAAA是真核生物mRNA多聚腺苷酸化位点中最高度保守的基序，在哺乳动物中，被多亚基CPSF（切割和多聚腺苷酸化特异性因子）复合物特异性识别。尽管CPSF在mRNA 3′端形成中具有重要功能，但其与AAUAAA相互作用的分子基础仍不清楚。CPSF亚基CPSF 160与AAUAAA识别有关，但缺乏直接证据。使用体外和体内测定，我们意外地发现CPSF亚基CPSF 30和Wdr 33直接接触AAUAAA。重要的是，CPSF 30-RNA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，其被流感蛋白NS 1A特异性靶向以抑制宿主mRNA 3′加工。我们的数据表明，哺乳动物mRNA 3′加工中的AAUAAA识别比以前认为的更复杂，涉及多种蛋白质-RNA相互作用。
AAUAAA is the most highly conserved motif in eukaryotic mRNA polyadenylation sites and, in mammals, is specifically recognized by the multisubunit CPSF complex. Chan et al. found that CPSF subunits CPSF30 and Wdr33 directly contact AAUAAA. 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. 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.
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