美国哈佛医学院Michael E. Greenberg等研究人员共同合作，探索出了人脑中RNA翻译的发展动力学。相关研究成果2022年9月28日在线发表于《自然—神经科学》杂志上。

研究人员对73例人类产前和成人皮质样本进行了核糖体分析。他们描述了被注释的开放阅读框（ORFs）的翻译调控，并确定了数千个以前未知的翻译事件，包括产生人类特异性和/或大脑特异性微蛋白的小ORFs，其中许多是他们用蛋白质组学独立验证的。在干细胞来源的人类神经元培养物的核糖体分析证实了这些发现，并发现几个神经元活动诱导的非编码RNA编码了以前未描述的微蛋白。对大脑微蛋白的物理化学分析发现了一类含有精氨酸-甘氨酸-甘氨酸(RGG)重复序列的蛋白质，它们可能是RNA代谢的调节因子。这一遗迹扩展了已知的人类大脑的翻译领域，并阐明了以前未知的大脑特异性蛋白产物。

据介绍，基因表达的精确调节是神经发育、可塑性和认知功能的基础。虽然有几项研究对发育中的人类大脑的转录进行了分析，但对伴随的翻译调节的理解仍有差距。

附：英文原文

Title: Developmental dynamics of RNA translation in the human brain

Author: Duffy, Erin E., Finander, Benjamin, Choi, GiHun, Carter, Ava C., Pritisanac, Iva, Alam, Aqsa, Luria, Victor, Karger, Amir, Phu, William, Sherman, Maxwell A., Assad, Elena G., Pajarillo, Naomi, Khitun, Alexandra, Crouch, Elizabeth E., Ganesh, Sanika, Chen, Jin, Berger, Bonnie, Sestan, Nenad, ODonnell-Luria, Anne, Huang, Eric J., Griffith, Eric C., Forman-Kay, Julie D., Moses, Alan M., Kalish, Brian T., Greenberg, Michael E.

Issue&Volume: 2022-09-28

Abstract: The precise regulation of gene expression is fundamental to neurodevelopment, plasticity and cognitive function. Although several studies have profiled transcription in the developing human brain, there is a gap in understanding of accompanying translational regulation. In this study, we performed ribosome profiling on 73 human prenatal and adult cortex samples. We characterized the translational regulation of annotated open reading frames (ORFs) and identified thousands of previously unknown translation events, including small ORFs that give rise to human-specific and/or brain-specific microproteins, many of which we independently verified using proteomics. Ribosome profiling in stem-cell-derived human neuronal cultures corroborated these findings and revealed that several neuronal activity-induced non-coding RNAs encode previously undescribed microproteins. Physicochemical analysis of brain microproteins identified a class of proteins that contain arginine-glycine-glycine (RGG) repeats and, thus, may be regulators of RNA metabolism. This resource expands the known translational landscape of the human brain and illuminates previously unknown brain-specific protein products.

DOI: 10.1038/s41593-022-01164-9

Source: https://www.nature.com/articles/s41593-022-01164-9