Identification of RNA recognition elements in the Saccharomyces cerevisiae transcriptome
Identification of RNA recognition elements in the Saccharomyces cerevisiae transcriptome
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DOI：
10.1093/nar/gkq920
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发表时间：
2011-03-01
影响因子：
14.9
通讯作者：
Brown, Patrick O.
中科院分区：
文献类型：
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作者：
Riordan, Daniel P.;Herschlag, Daniel;Brown, Patrick O.
基因表达的转录后调控，包括mRNA的定位、翻译和降解，是普遍存在的，但在很大程度上仍未被探索。每个mRNA的转录后调控程序是如何在其序列中编码的？数以百计的特异性RNA结合蛋白（RBP）似乎在介导转录后调控程序中发挥作用，类似于特异性DNA结合蛋白在转录中的作用。作为解码每个mRNA中编码的调控程序的一步，我们专注于特定的mRNA-蛋白质相互作用。我们通过计算分析了29个特定RBP在体内结合的酿酒酵母mRNA序列，确定了8个新的候选基序，并确认或扩展了6个早期报道的识别元件。对12种酵母RBP选择性识别的RNA序列进行生物化学选择，得到了Pin 4、Nsr 1、Hrb 1、Gbp 2、Sgn 1和Mrn 1结合的新基序，并回收了已知的Puf 3、She 2、Vts 1和Whi 3识别元件。我们发现的大多数RNA元件与连贯的mRNA表达变化相关，并且在相关酵母中显着保守，支持其功能重要性，并表明相应的RNA-蛋白质相互作用在进化上是保守的。
Post-transcriptional regulation of gene expression, including mRNA localization, translation and decay, is ubiquitous yet still largely unexplored. How is the post-transcriptional regulatory program of each mRNA encoded in its sequence? Hundreds of specific RNA-binding proteins (RBPs) appear to play roles in mediating the post-transcriptional regulatory program, akin to the roles of specific DNA-binding proteins in transcription. As a step toward decoding the regulatory programs encoded in each mRNA, we focused on specific mRNA-protein interactions. We computationally analyzed the sequences of Saccharomyces cerevisiae mRNAs bound in vivo by 29 specific RBPs, identifying eight novel candidate motifs and confirming or extending six earlier reported recognition elements. Biochemical selections for RNA sequences selectively recognized by 12 yeast RBPs yielded novel motifs bound by Pin4, Nsr1, Hrb1, Gbp2, Sgn1 and Mrn1, and recovered the known recognition elements for Puf3, She2, Vts1 and Whi3. Most of the RNA elements we uncovered were associated with coherent mRNA expression changes and were significantly conserved in related yeasts, supporting their functional importance and suggesting that the corresponding RNA-protein interactions are evolutionarily conserved.