Global signatures of protein binding on structured RNAs in Saccharomyces cerevisiae
Global signatures of protein binding on structured RNAs in Saccharomyces cerevisiae
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DOI：
10.1007/s11427-013-4583-0
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发表时间：
2013-12
期刊：
影响因子：
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通讯作者：
Yucheng T. Yang;Jumpei Umetsu;Z. Lu
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文献类型：
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作者：
Yucheng T. Yang;Jumpei Umetsu;Z. Lu
蛋白质结合对几乎所有RNA分子的运输、衰变和调节都是必不可少的。然而，蛋白质结合rna的结构偏好及其在变化的环境条件下的细胞功能和动力学尚不清楚。在这里，我们整合了各种高通量数据，并引入了一个计算框架，以单核苷酸分辨率描述酵母中RNA结合蛋白（rbp）和结构RNA之间的全局相互作用。我们发现，平均而言，就总长度的百分比而言，约15%的mRNA非翻译区（utr），约37%的典型非编码rna （ncRNAs）和约11%的长ncRNAs （lncRNAs）被蛋白质结合。一般来说，RBP结合位点倾向于出现在单链环上，具有进化保守的特征，并且通常在体内促进特定的RNA结构构象。我们发现tRNA的四个核苷酸修饰与RBP结合显著相关。我们还在mrna的utr中发现了rbp结合的各种结构基序，这些结构基序与定位、降解和应激反应有关。此外，我们鉴定了200个与rbp结合的新型lncrna，其中约一半含有保守的二级结构。我们提出了真核生物基因组结构非编码区RBP结合位点的第一个集合模式，强调了它们的结构背景和细胞功能。
Protein binding is essential to the transport, decay and regulation of almost all RNA molecules. However, the structural preference of protein binding on RNAs and their cellular functions and dynamics upon changing environmental conditions are poorly understood. Here, we integrated various high-throughput data and introduced a computational framework to describe the global interactions between RNA binding proteins (RBPs) and structured RNAs in yeast at single-nucleotide resolution. We found that on average, in terms of percent total lengths, ∼15% of mRNA untranslated regions (UTRs), ∼37% of canonical non-coding RNAs (ncRNAs) and ∼11% of long ncRNAs (lncRNAs) are bound by proteins. The RBP binding sites, in general, tend to occur at single-stranded loops, with evolutionarily conserved signatures, and often facilitate a specific RNA structure conformation in vivo. We found that four nucleotide modifications of tRNA are significantly associated with RBP binding. We also identified various structural motifs bound by RBPs in the UTRs of mRNAs, associated with localization, degradation and stress responses. Moreover, we identified >200 novel lncRNAs bound by RBPs, and about half of them contain conserved secondary structures. We present the first ensemble pattern of RBP binding sites in the structured non-coding regions of a eukaryotic genome, emphasizing their structural context and cellular functions.