CAF1 plays an important role in mRNA deadenylation separate from its contact to CCR4.
CAF1 plays an important role in mRNA deadenylation separate from its contact to CCR4.
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DOI：
10.1093/nar/gkm196
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发表时间：
2007
影响因子：
14.9
通讯作者：
Denis CL
中科院分区：
文献类型：
--
作者：
Ohn T;Chiang YC;Lee DJ;Yao G;Zhang C;Denis CL
CAF 1蛋白是CCR 4-NOT去腺苷酶复合物的一个组分。虽然酵母CAF 1显示去腺苷酶活性，但这种活性不是其体内去腺苷化功能所必需的，并且CCR 4是复合物中的主要去腺苷酶。为了确定CAF 1的特异性功能区所需的脱氧腺苷在体内，我们有针对性地诱变CAF 1的6个区域，是CAF 1的直系同源物之间的具体保守。发现残基213-215中的缺陷是结合CCR 4所需的位点，其在较小程度上降低了去腺苷化的速率，并且导致体内表型的严重程度低于CAF 1的其他区域中的缺陷，所述CAF 1的其他区域显示出与CCR 4更大的接触。这些结果表明，CAF 1，而影响去腺苷化通过其接触CCR 4，具有功能，在去腺苷化分离其接触CCR 4。caf 1 Δ的合成致死性，而不是ccr 4 Δ的合成致死性，具有DHH 1或PAB 1的缺陷，这两者都参与翻译，进一步支持CAF 1的作用与CCR 4的作用不同。重要的是，PAB 1中其他减少翻译的突变，虽然本身或与ccr 4 Δ组合时不影响去腺苷化，但当与caf 1缺失结合时，会严重阻断去腺苷化。这些结果表明CAF 1和参与翻译的因子都是去腺苷化所必需的。
The CAF1 protein is a component of the CCR4–NOT deadenylase complex. While yeast CAF1 displays deadenylase activity, this activity is not required for its deadenylation function in vivo, and CCR4 is the primary deadenylase in the complex. In order to identify CAF1-specific functional regions required for deadenylation in vivo, we targeted for mutagenesis six regions of CAF1 that are specifically conserved among CAF1 orthologs. Defects in residues 213–215, found to be a site required for binding CCR4, reduced the rate of deadenylation to a lesser extent and resulted in in vivo phenotypes that were less severe than did defects in other regions of CAF1 that displayed greater contact to CCR4. These results imply that CAF1, while affecting deadenylation through its contact to CCR4, has functions in deadenylation separate from its contact to CCR4. Synthetic lethalities of caf1Δ, but not that of ccr4Δ, with defects in DHH1 or PAB1, both of which are involved in translation, further supports a role of CAF1 separate from that of CCR4. Importantly, other mutations in PAB1 that reduced translation, while not affecting deadenylation by themselves or when combined with ccr4Δ, severely blocked deadenylation when coupled with a caf1 deletion. These results indicate that both CAF1 and factors involved in translation are required for deadenylation.
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影响因子：
64.8
作者：
Gavin, AC;Bösche, M;Superti-Furga, G
通讯作者：
Superti-Furga, G
影响因子：
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作者：
Cui, YJ;Denis, CL
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Denis, CL
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14.9
作者：
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Sachs, AB
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作者：
Dlakic, M
通讯作者：
Dlakic, M