Whi3, a developmental regulator of budding yeast, binds a large set of mRNAs functionally related to the endoplasmic reticulum
Whi3, a developmental regulator of budding yeast, binds a large set of mRNAs functionally related to the endoplasmic reticulum
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DOI：
10.1074/jbc.m804604200
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发表时间：
2008-10-17
影响因子：
4.8
通讯作者：
Gari, Eloi
中科院分区：
文献类型：
--
作者：
Colomina, Neus;Ferrezuelo, Francisco;Gari, Eloi
Whi 3是与内质网（ER）相关的RNA结合蛋白，其结合CLN 3 mRNA，并在细胞周期蛋白Cln 3在ER的有效保留中起关键作用。在目前的工作中，我们已经确定了新的Whi 3相关的mRNA的基因组方法。这些Whi 3靶标中的大量和显著数量编码参与诸如运输和细胞壁生物发生的过程的膜和胞吐蛋白。与基因组数据一致，我们观察到细胞壁完整性在Whi 3缺陷细胞中受损，并发现Whi 3与细胞完整性途径之间存在强烈的遗传相互作用。Whi 3相关的mRNA富含四核苷酸GCAU簇，CLN 3 mRNA中GCAU簇的突变导致其与Whi 3的关联减少，表明这些序列可能作为结合的顺式决定簇。我们的数据表明，Whi 3参与调节和/或本地化的功能相关的ER的mRNA的一个大的子集，因为它是重要的不同的分子过程，如细胞质滞留或胞外交通的蛋白质，我们建议Whi 3是一个通用的调制器的蛋白质命运在芽殖酵母。
Whi3 is an RNA-binding protein associated with the endoplasmic reticulum (ER) that binds the CLN3 mRNA and plays a key role in the efficient retention of cyclin Cln3 at the ER. In the present work, we have identified new Whi3-associated mRNAs by a genomic approach. A large and significant number of these Whi3 targets encode for membrane and exocytic proteins involved in processes such as transport and cell wall biogenesis. Consistent with the genomic data, we have observed that cell wall integrity is compromised in Whi3-deficient cells and found strong genetic interactions between WHI3 and the cell integrity pathway. Whi3-associated mRNAs are enriched in clusters of the tetranucleotide GCAU, and mutation of the GCAU clusters in the CLN3 mRNA caused a reduction in its association to Whi3, suggesting that these sequences may act as cis-determinants for binding. Our data suggest that Whi3 is involved in the regulation and/or localization of a large subset of mRNAs functionally related to the ER and, since it is important for different molecular processes such as cytoplasmic retention or exocytic traffic of proteins, we propose that Whi3 is a general modulator of protein fate in budding yeast.