RNA-dependent integrin α3 protein localization regulated by the Muscleblind-like protein MLP1

RNA-dependent integrin α3 protein localization regulated by the Muscleblind-like protein MLP1
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DOI:
10.1038/ncb1335
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发表时间:
2005-12-01
影响因子:
21.3
通讯作者:
Hsu, T
Hsu, T
中科院分区:
生物学1区
文献类型:
--
作者:
Adereth, Y;Dammai, V;Hsu, T

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我们发现,整合素α(3)蛋白的局部表达在RNA定位水平上受到果蝇肌盲的人类同源物MLP 1/MBLL/MBNL 2(一种独特的Cys(3)His锌指蛋白)的调控。这得到了以下观察结果的支持:MLP 1敲低消除了整合素α(3)在粘附复合物上的定位; MLP 1定位在含有磷酸化粘着斑激酶的粘附斑中;这种定位是微管依赖性的;整合素α(3)转录物与MLP 1共定位在不同的细胞质基因座中;整合素α(3)转录物在细胞中与MLP 1物理结合,并且MLP 1在体外与整合素α(3)3'非翻译区(UTR)中的特异性ACACCC基序结合;而绿色荧光蛋白(GFP)开放阅读框-整联蛋白α(3)3' UTR嵌合基因指导GFP蛋白定位于细胞周边附近的不同细胞质位点,其依赖于MLP 1并由ACACCC基序介导,但不依赖于整联蛋白α(3)信号肽。
We show that localized expression of the integrin alpha(3) protein is regulated at the level of RNA localization by the human homologue of Drosophila Muscleblind, MLP1/MBLL/MBNL2, a unique Cys(3)His zinc-finger protein. This is supported by the following observations: MLP1 knockdown abolishes localization of integrin alpha(3) to the adhesion complexes; MLP1 is localized in adhesion plaques that contain phospho-focal adhesion kinase; this localization is microtubule-dependent; integrin alpha(3) transcripts colocalize with MLP1 in distinct cytoplasmic loci; integrin alpha(3) transcripts are physically associated with MLP1 in cells and MLP1 binds to a specific ACACCC motif in the integrin alpha(3) 3' untranslated region (UTR) in vitro; and a green fluorescent protein (GFP) open reading frame-integrin alpha(3) 3' UTR chimeric gene directs GFP protein localization to distinct cytoplasmic loci near the cell periphery, which is dependent on MLP1 and is mediated by the ACACCC motif but is independent of the integrin alpha(3) signal peptide.