Messenger RNA

Translation (biology)

Transcriptome

Neuroscience

Ribosome profiling

Open reading frame

Biology

Gene

Gene expression

Peptide sequence

Human brain

RNA-binding protein

ORFS

Computational biology

Translational regulation

Genetics

Nature Neuroscience

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. Duffy et al. profiled mRNA translation in 73 human prenatal and adult cortex samples and identified thousands of previously unknown translation events, including small open reading frames that give rise to human-specific and/or brain-specific microproteins.

Developmental dynamics of RNA translation in the human brain