A conserved CCCH-type zinc finger protein regulates mRNA nuclear adenylation and export.
A conserved CCCH-type zinc finger protein regulates mRNA nuclear adenylation and export.
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DOI：
10.1083/jcb.200811072
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发表时间：
2009-04-20
期刊：
影响因子：
--
通讯作者：
Silver PA
中科院分区：
文献类型：
--
作者：
Hurt JA;Obar RA;Zhai B;Farny NG;Gygi SP;Silver PA
信使RNA （mRNA）核输出与先前处理步骤的耦合有助于mRNA转运到细胞质的保真度和效率。在本研究中，我们发现输出和聚腺苷化过程通过黑腹果蝇ccch型锌指蛋白CG6694/dZC3H3通过物理和功能相互作用耦合。我们发现，S2R+细胞中dZC3H3的缺失导致转录物高腺苷化。利用靶向共免疫沉淀和液相色谱质谱(MS)/MS技术，我们表征了mRNA核输出和聚腺苷酸化机制的已知组分与dZC3H3的相互作用。此外，我们证明了该因子的功能守恒，因为小干扰RNA消耗其人类同源物ZC3H3也会导致人类细胞中mRNA输出缺陷。在缺乏zc3h3的细胞中，核聚腺苷化（poly(A)） RNA被隔离在从含有sc35的斑点中移除的病灶中，表明poly(A) RNA的正常亚核分布发生了变化。我们的数据提出了一个模型，其中ZC3H3在聚腺苷化机制，新聚(a) mrna和转录输出因子之间的界面。
Coupling of messenger RNA (mRNA) nuclear export with prior processing steps aids in the fidelity and efficiency of mRNA transport to the cytoplasm. In this study, we show that the processes of export and polyadenylation are coupled via the Drosophila melanogaster CCCH-type zinc finger protein CG6694/dZC3H3 through both physical and functional interactions. We show that depletion of dZC3H3 from S2R+ cells results in transcript hyperadenylation. Using targeted coimmunoprecipitation and liquid chromatography mass spectrometry (MS)/MS techniques, we characterize interactions of known components of the mRNA nuclear export and polyadenylation machineries with dZC3H3. Furthermore, we demonstrate the functional conservation of this factor, as depletion of its human homologue ZC3H3 by small interfering RNA results in an mRNA export defect in human cells as well. Nuclear polyadenylated (poly(A)) RNA in ZC3H3-depleted cells is sequestered in foci removed from SC35-containing speckles, indicating a shift from the normal subnuclear distribution of poly(A) RNA. Our data suggest a model wherein ZC3H3 interfaces between the polyadenylation machinery, newly poly(A) mRNAs, and factors for transcript export.
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影响因子：
4.5
作者：
Brodsky, AS;Silver, PA
通讯作者：
Silver, PA
poly（a）RNA的离散核域及其与核的功能组织的关系。
影响因子：
7.8
作者：
Carter, K C;Taneja, K L;Lawrence, J B
通讯作者：
Lawrence, J B
影响因子：
11.4
作者：
BIENROTH, S;KELLER, W;WAHLE, E
通讯作者：
WAHLE, E
影响因子：
64.5
作者：
Cheng, Hong;Dufu, Kobina;Reed, Robin
通讯作者：
Reed, Robin
影响因子：
16
作者：
Huang, YQ;Gattoni, R;Steitz, JA
通讯作者：
Steitz, JA