NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif.
NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif.
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DOI：
10.1093/nar/gkp861
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发表时间：
2010-01
影响因子：
14.9
通讯作者：
Gorospe M
中科院分区：
文献类型：
--
作者：
Kuwano Y;Pullmann R Jr;Marasa BS;Abdelmohsen K;Lee EK;Yang X;Martindale JL;Zhan M;Gorospe M
RNA结合蛋白核因子90（NF 90）参与了多种靶mRNA的稳定、转运和翻译控制。然而，尚未进行NF 90靶mRNA的系统分析。在这里，我们使用核糖核蛋白免疫沉淀分析，以确定一个大子集的NF 90相关的mRNA。这些mRNA的3′-非翻译区（UTR）的比较导致了一个25- 30个核苷酸的，富含腺嘌呤和尿嘧啶的RNA签名基序的阐明。在EGFP异源报告基因的3′UTR中插入富含AU的NF 90基序（“NF 90 m”）不会影响嵌合EGFP-NF 90 m mRNA的稳态水平或其胞质丰度。相反，EGFP-NF 90 m mRNA的翻译被特异性地抑制在NF 90依赖的方式，如通过分析新生的EGFP翻译，嵌合mRNA在多核糖体梯度上的分布和表达的EGFP蛋白的稳态水平所确定的。在测试内源性mRNA和含有NF 90基序命中的重组生物素化转录物后，验证内源性NF 90与靶mRNA的相互作用。进一步的分析表明，内源性NF 90靶mRNA的稳定性不受NF 90丰度的显著影响，而当NF 90水平降低时，它们的翻译增加。总之，我们已经鉴定了NF 90靶mRNA中存在的富含AU的RNA基序，并且已经获得了NF 90抑制该mRNA子集的翻译的证据。
The RNA-binding protein nuclear factor 90 (NF90) has been implicated in the stabilization, transport and translational control of several target mRNAs. However, a systematic analysis of NF90 target mRNAs has not been performed. Here, we use ribonucleoprotein immunoprecipitation analysis to identify a large subset of NF90-associated mRNAs. Comparison of the 3′-untranslated regions (UTRs) of these mRNAs led to the elucidation of a 25- to 30-nucleotide, RNA signature motif rich in adenines and uracils. Insertion of the AU-rich NF90 motif (‘NF90m’) in the 3′UTR of an EGFP heterologous reporter did not affect the steady-state level of the chimeric EGFP-NF90m mRNA or its cytosolic abundance. Instead, the translation of EGFP-NF90m mRNA was specifically repressed in an NF90-dependent manner, as determined by analysing nascent EGFP translation, the distribution of chimeric mRNAs on polysome gradients and the steady-state levels of expressed EGFP protein. The interaction of endogenous NF90 with target mRNAs was validated after testing both endogenous mRNAs and recombinant biotinylated transcripts containing NF90 motif hits. Further analysis showed that the stability of endogenous NF90 target mRNAs was not significantly influenced by NF90 abundance, while their translation increased when NF90 levels were reduced. In summary, we have identified an AU-rich RNA motif present in NF90 target mRNAs and have obtained evidence that NF90 represses the translation of this subset of mRNAs.
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DOI：
10.1073/pnas.95.15.8514
发表时间：
1998-07-21
影响因子：
11.1
作者：
Liao, HJ;Kobayashi, R;Mathews, MB
通讯作者：
Mathews, MB
影响因子：
16.8
作者：
Liao, Baisong;Hu, Yan;Brewer, Gary
通讯作者：
Brewer, Gary
影响因子：
5.3
作者：
Galban, Stefanie;Kuwano, Yuki;Gorospe, Myriam
通讯作者：
Gorospe, Myriam
影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
11.4
作者：
Lee, Y;Hur, I;Kim, VN
通讯作者：
Kim, VN