美国西北大学Richard W. Carthew和Luis A. Nunes Amaral研究小组合作报道抑制性基因调控能够将发育与细胞代谢同步化。这一研究成果于2019年8月9日发表在国际顶尖学术期刊《细胞》上。

研究人员发现基因的分层抑制将GRN输出与可变代谢相结合。当转录抑制因子或mRNA和蛋白质稳定性丧失时，果蝇发育中的错误会在代谢降低时减少。通过去除抑制因子的整个microRNA家族，研究人员证明了这种现象的普遍性，并发现当代谢降低时，成熟的发育可以在很大程度上得到挽回。使用模拟GRN动态的数学模型，研究人员发现降低代谢可以通过减少辅助抑制因子对GRN输出的影响，来抑制发育错误的出现。研究人员通过实验证明，当代谢降低时，基因表达的动态性将更少地受到抑制因子缺失的影响。因此，分层抑制通过错误抑制为发育提供了稳健性，并且可能为更短的生殖周期提供进化路线。

据介绍，代谢条件影响动物的发育速度。因此，发育基因调控网络（GRN）必须使其动态与变化的时间尺度同步。

附：英文原文

Title: Repressive Gene Regulation Synchronizes Development with Cellular Metabolism

Author: Justin J. Cassidy, Sebastian M. Bernasek, Rachael Bakker, Ritika Giri, Nicolás Peláez, Bryan Eder, Anna Bobrowska, Neda Bagheri, Luis A. Nunes Amaral, Richard W. Carthew

Issue&Volume: Volume 178 Issue 4

Abstract: Metabolic conditions affect the developmental tempo of animals. Developmental gene regulatory networks (GRNs) must therefore synchronize their dynamics with a variable timescale. We find that layered repression of genes couples GRN output with variable metabolism. When repressors of transcription or mRNA and protein stability are lost, fewer errors in Drosophila development occur when metabolism is lowered. We demonstrate the universality of this phenomenon by eliminating the entire microRNA family of repressors and find that development to maturity can be largely rescued when metabolism is reduced. Using a mathematical model that replicates GRN dynamics, we find that lowering metabolism suppresses the emergence of developmental errors by curtailing the influence of auxiliary repressors on GRN output. We experimentally show that gene expression dynamics are less affected by loss of repressors when metabolism is reduced. Thus, layered repression provides robustness through error suppression and may provide an evolutionary route to a shorter reproductive cycle.

DOI: https://doi.org/10.1016/j.cell.2019.06.023

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30686-5