Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
Mol Cell. 2012 Oct 26;48(2):169-81. doi: 10.1016/j.molcel.2012.08.008. Epub 2012 Sep 13.
RNA structural transitions are important in the function and regulation of RNAs. Here, we reveal a layer of transcriptome organization in the form of RNA folding energies. By probing yeast RNA structures at different temperatures, we obtained relative melting temperatures (Tm) for RNA structures in over 4000 transcripts. Specific signatures of RNA Tm demarcated the polarity of mRNA open reading frames and highlighted numerous candidate regulatory RNA motifs in 3' untranslated regions. RNA Tm distinguished noncoding versus coding RNAs and identified mRNAs with distinct cellular functions. We identified thousands of putative RNA thermometers, and their presence is predictive of the pattern of RNA decay in vivo during heat shock. The exosome complex recognizes unpaired bases during heat shock to degrade these RNAs, coupling intrinsic structural stabilities to gene regulation. Thus, genome-wide structural dynamics of RNA can parse functional elements of the transcriptome and reveal diverse biological insights.
RNA 结构转变在 RNA 的功能和调控中很重要。在这里,我们以 RNA 折叠能的形式揭示了转录组组织的一个层次。通过在不同温度下探测酵母 RNA 结构,我们获得了 4000 多个转录本中 RNA 结构的相对熔点 (Tm)。RNA Tm 的特定特征划定了 mRNA 开放阅读框的极性,并突出了 3'非翻译区中许多候选调控 RNA 基序。RNA Tm 将非编码 RNA 与编码 RNA 区分开来,并鉴定了具有不同细胞功能的 mRNA。我们鉴定了数千个潜在的 RNA 温度计,其存在可预测热休克过程中体内 RNA 衰减的模式。外切体复合物在热休克期间识别未配对的碱基,以降解这些 RNA,将内在结构稳定性与基因调控联系起来。因此,RNA 的全基因组结构动力学可以解析转录组的功能元件,并揭示多种生物学见解。