A single spacer nucleotide determines the specificities of two mRNA regulatory proteins

A single spacer nucleotide determines the specificities of two mRNA regulatory proteins
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DOI:
10.1038/nsmb1010
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发表时间:
2005-11-01
影响因子:
16.8
通讯作者:
Wickens, M
Wickens, M
中科院分区:
生物学1区
文献类型:
--
作者:
Opperman, L;Hook, B;Wickens, M

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信使 RNA 的调节在许多情况下都至关重要,包括发育、记忆和细胞生长。 3'非翻译区是结合蛋白质和 microRNA 的丰富调控元件库。在这里,我们重点关注 PUF 蛋白,这是一个重要的 mRNA 调节蛋白家族,对干细胞增殖、模式形成和突触可塑性至关重要。我们发现两种秀丽隐杆线虫 PUF 蛋白 FBF 和 PUF-8 在 RNA 结合特异性方面存在差异。 FBF 要求在八个核苷酸位点的中间存在一个“额外”核苷酸,而 PUF-8 则要求不存在该核苷酸。一个离散的蛋白质片段造成了这种差异。我们认为 FBF 中心区域的结构扭曲需要额外的核苷酸,并且这种 PUF 特异性模式可能很常见。我们建议可以使用 PUF 支架设计和选择新的特异性。
Regulation of messenger RNA is crucial in many contexts, including development, memory and cell growth. The 3' untranslated region is a rich repository of regulatory elements that bind proteins and microRNAs. Here we focus on PUF proteins, an important family of mRNA regulatory proteins crucial in stem-cell proliferation, pattern formation and synaptic plasticity. We show that two Caenorhabditis elegans PUF proteins, FBF and PUF-8, differ in RNA-binding specificity. FBF requires the presence of a single 'extra' nucleotide in the middle of an eight-nucleotide site, whereas PUF-8 requires its absence. A discrete protein segment is responsible for the difference. We propose that a structural distortion in the central region of FBF imposes the requirement for the additional nucleotide and that this mode of PUF specificity may be common. We suggest that new specificities can be designed and selected using the PUF scaffold.