Developmental dynamics of RNA translation in the human brain

Erin E. Duffy, Benjamin Finander, Gi Hun Choi, Ava C. Carter, Iva Pritisanac, Aqsa Alam, Victor Luria, Amir Karger, William Phu, Maxwell A. Sherman, Elena G. Assad, Naomi Pajarillo, Alexandra Khitun, Elizabeth E. Crouch, Sanika Ganesh, Jin Chen, Bonnie Berger, Nenad Sestan, Anne O’Donnell-Luria, Eric J. HuangEric C. Griffith, Julie D. Forman-Kay, Alan M. Moses, Brian T. Kalish, Michael E. Greenberg

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1353-1365
Number of pages13
JournalNature neuroscience
Issue number10
StatePublished - Oct 2022

ASJC Scopus subject areas

  • Neuroscience(all)


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