Structural basis for polyadenosine-RNA binding by Nab2 Zn fingers and its function in mRNA nuclear export.
Structural basis for polyadenosine-RNA binding by Nab2 Zn fingers and its function in mRNA nuclear export.
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DOI：
10.1016/j.str.2012.03.011
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发表时间：
2012-06-06
期刊：
影响因子：
5.7
通讯作者：
Stewart, Murray
中科院分区：
文献类型：
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作者：
Brockmann, Christoph;Soucek, Sharon;Kuhlmann, Sonja I.;Mills-Lujan, Katherine;Kelly, Seth M.;Yang, Ji-Chun;Iglesias, Nahid;Stutz, Francoise;Corbett, Anita H.;Neuhaus, David;Stewart, Murray
成熟mRNPs的聚腺苷化调控和有效的核输出都需要含有7个CCCH锌指的聚腺苷- rna结合蛋白Nab2。我们描述了手指5-7的溶液结构，这是高亲和力聚腺苷- rna结合所必需的和充分的，并确定了关键残基。这些锌指形成一个单一的结构单元。在RNA结合受损的Nab2-C437S突变体中，结构一致性丢失，该突变体也抑制RNA解旋酶Dbp5的rat8-2等位基因。结构导向的Nab2变异表明，dbp5（rat8-2）的抑制与核RNA输出接头Yra1的高腺苷化和突变等位基因的抑制更密切相关，而不是与聚腺苷-RNA的亲和力有关。这些结果表明，除了调节polyA尾部长度外，Nab2还具有与产生输出能力mRNP相关的意想不到的功能，并且手指5-7内的变化导致mRNP输出复合物的次优组装，这些复合物在到达细胞质后更容易被Dbp5分解。►Nab2锌指5-7具有不寻常的连贯结构►Nab2在出口能力mRNPs的组装中具有意想不到的作用►核磁共振鉴定出结合聚腺苷的Nab2残基►结构引导突变表明Nab2在基因表达途径中的功能
Polyadenylation regulation and efficient nuclear export of mature mRNPs both require the polyadenosine-RNA-binding protein, Nab2, which contains seven CCCH Zn fingers. We describe here the solution structure of fingers 5-7, which are necessary and sufficient for high-affinity polyadenosine-RNA binding, and identify key residues involved. These Zn fingers form a single structural unit. Structural coherence is lost in the RNA-binding compromised Nab2-C437S mutant, which also suppresses the rat8-2 allele of RNA helicase Dbp5. Structure-guided Nab2 variants indicate that dbp5(rat8-2) suppression is more closely linked to hyperadenylation and suppression of mutant alleles of the nuclear RNA export adaptor, Yra1, than to affinity for polyadenosine-RNA. These results indicate that, in addition to modulating polyA tail length, Nab2 has an unanticipated function associated with generating export-competent mRNPs, and that changes within fingers 5-7 lead to suboptimal assembly of mRNP export complexes that are more easily disassembled by Dbp5 upon reaching the cytoplasm. ► Nab2 Zn fingers 5-7 have an unusual coherent structure ► Nab2 has an unanticipated role in assembly of export-competent mRNPs ► NMR identifies Nab2 residues that bind polyadenosine ► Structure-guided mutants indicate Nab2's function in the gene expression pathway
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影响因子：
16
作者：
Johnson, Sara Ann;Cubberley, Gabrielle;Bentley, David L.
通讯作者：
Bentley, David L.
DOI：
10.1074/jbc.m110.141127
发表时间：
2010-08-20
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kelly SM;Leung SW;Apponi LH;Bramley AM;Tran EJ;Chekanova JA;Wente SR;Corbett AH
通讯作者：
Corbett AH
影响因子：
21.3
作者：
Alcazar-Roman, Abel R.;Tran, Elizabeth J.;Wente, Susan R.
通讯作者：
Wente, Susan R.
DOI：
10.1107/s0907444994010723
发表时间：
1995-03-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
DIAMOND, R
通讯作者：
DIAMOND, R
影响因子：
16.8
作者：
通讯作者：
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