Xue Shifeng, Tian Siqi, Fujii Kotaro, Kladwang Wipapat, Das Rhiju, Barna Maria
1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA [3] Tetrad Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA.
Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
Nature. 2015 Jan 1;517(7532):33-8. doi: 10.1038/nature14010. Epub 2014 Nov 19.
Emerging evidence suggests that the ribosome has a regulatory function in directing how the genome is translated in time and space. However, how this regulation is encoded in the messenger RNA sequence remains largely unknown. Here we uncover unique RNA regulons embedded in homeobox (Hox) 5' untranslated regions (UTRs) that confer ribosome-mediated control of gene expression. These structured RNA elements, resembling viral internal ribosome entry sites (IRESs), are found in subsets of Hox mRNAs. They facilitate ribosome recruitment and require the ribosomal protein RPL38 for their activity. Despite numerous layers of Hox gene regulation, these IRES elements are essential for converting Hox transcripts into proteins to pattern the mammalian body plan. This specialized mode of IRES-dependent translation is enabled by an additional regulatory element that we term the translation inhibitory element (TIE), which blocks cap-dependent translation of transcripts. Together, these data uncover a new paradigm for ribosome-mediated control of gene expression and organismal development.
新出现的证据表明，核糖体在指导基因组如何在时间和空间上进行翻译方面具有调节功能。然而，这种调节如何编码在信使RNA序列中在很大程度上仍然未知。在这里，我们发现了嵌入在同源框（Hox）5'非翻译区（UTR）中的独特RNA调控子，它们赋予核糖体介导的基因表达控制。这些结构化RNA元件类似于病毒内部核糖体进入位点（IRES），存在于Hox mRNA的子集中。它们促进核糖体招募，并且其活性需要核糖体蛋白RPL38。尽管Hox基因存在多层调控，但这些IRES元件对于将Hox转录本转化为蛋白质以塑造哺乳动物身体结构至关重要。这种依赖IRES的特殊翻译模式由我们称为翻译抑制元件（TIE）的额外调控元件实现，该元件阻断转录本的帽依赖性翻译。总之，这些数据揭示了核糖体介导的基因表达和生物体发育控制的新范式。
