학술논문

Developmental dynamics of RNA translation in the human brain
Document Type
article
Source
Nature Neuroscience. 25(10)
Subject
Biological Psychology
Biomedical and Clinical Sciences
Neurosciences
Psychology
Stem Cell Research - Induced Pluripotent Stem Cell - Human
Stem Cell Research - Induced Pluripotent Stem Cell
Stem Cell Research - Nonembryonic - Human
Genetics
Biotechnology
Stem Cell Research
Underpinning research
1.1 Normal biological development and functioning
Neurological
Adult
Arginine
Brain
Gene Expression Regulation
Glycine
Humans
Protein Biosynthesis
RNA
Messenger
Cognitive Sciences
Neurology & Neurosurgery
Biological psychology
Language
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.