Castelo-Szekely Violeta, Arpat Alaaddin Bulak, Janich Peggy, Gatfield David
Center for Integrative Genomics, University of Lausanne, Génopode, 1015, Lausanne, Switzerland.
Vital-IT, Swiss Institute of Bioinformatics, Génopode, 1015, Lausanne, Switzerland.
Genome Biol. 2017 Jun 16;18(1):116. doi: 10.1186/s13059-017-1222-2.
The daily gene expression oscillations that underlie mammalian circadian rhythms show striking differences between tissues and involve post-transcriptional regulation. Both aspects remain poorly understood. We have used ribosome profiling to explore the contribution of translation efficiency to temporal gene expression in kidney and contrasted our findings with liver data available from the same mice.
Rhythmic translation of constantly abundant messenger RNAs (mRNAs) affects largely non-overlapping transcript sets with distinct phase clustering in the two organs. Moreover, tissue differences in translation efficiency modulate the timing and amount of protein biosynthesis from rhythmic mRNAs, consistent with organ specificity in clock output gene repertoires and rhythmicity parameters. Our comprehensive datasets provided insights into translational control beyond temporal regulation. Between tissues, many transcripts show differences in translation efficiency, which are, however, of markedly smaller scale than mRNA abundance differences. Tissue-specific changes in translation efficiency are associated with specific transcript features and, intriguingly, globally counteracted and compensated transcript abundance variations, leading to higher similarity at the level of protein biosynthesis between both tissues.
We show that tissue specificity in rhythmic gene expression extends to the translatome and contributes to define the identities, the phases and the expression levels of rhythmic protein biosynthesis. Moreover, translational compensation of transcript abundance divergence leads to overall higher similarity at the level of protein production across organs. The unique resources provided through our study will serve to address fundamental questions of post-transcriptional control and differential gene expression in vivo.
构成哺乳动物昼夜节律的每日基因表达振荡在不同组织之间表现出显著差异，并且涉及转录后调控。这两个方面目前仍了解甚少。我们利用核糖体谱分析来探究翻译效率对肾脏中基因表达时间性的贡献，并将我们的研究结果与来自同一小鼠的肝脏数据进行对比。
持续丰富的信使核糖核酸（mRNA）的节律性翻译在很大程度上影响两个器官中互不重叠的转录本组，且具有不同的相位聚类。此外，翻译效率的组织差异调节了有节律的mRNA的蛋白质生物合成的时间和量，这与时钟输出基因库和节律性参数中的器官特异性一致。我们全面的数据集为超越时间调控的翻译控制提供了见解。在不同组织之间，许多转录本在翻译效率上存在差异，然而其规模明显小于mRNA丰度差异。翻译效率的组织特异性变化与特定的转录本特征相关，有趣的是，它在整体上抵消并补偿了转录本丰度的变化，从而导致两个组织在蛋白质生物合成水平上具有更高的相似性。
我们表明，节律性基因表达中的组织特异性延伸到翻译组，并有助于定义节律性蛋白质生物合成的特性、相位和表达水平。此外，请转录本丰度差异的翻译补偿导致各器官在蛋白质产生水平上总体具有更高的相似性。我们的研究所提供的独特资源将有助于解决体内转录后控制和基因表达差异方面的基本问题。
