Pervasive functional translation of noncanonical human open reading frames

Abstract

Using mass spectrometry, ribosome profiling, and several CRISPR-based screens, Chen et al. identified hundreds of previously uncharacterized functional micropeptides in the human genome (see the Perspective by Wei and Guo). Protein translation outside of annotated open reading frames (ORFs) in messenger RNAs and within ORFs in long noncoding RNAs is pervasive. A functional screen using CRISPR-Cas9 with single-cell transcriptomics suggested critical roles for hundreds of micropeptides. Micropeptides encoded by multiple short, upstream ORFs form stable protein complexes with the downstream canonical proteins encoded on the same messenger RNAs.

Document Details

Document Type
Pub Defense Publication
Publication Date
Mar 06, 2020
Source ID
10.1126/science.aay0262

Entities

People

  • Alexander P. Fields
  • Andreas-David Brunner
  • Britt Adamson
  • Daniel N Itzhak
  • J. Zachery Cogan
  • James K Nuñez
  • Jason Y. Li
  • Jin Chen
  • Jonathan Weissman
  • Manuel D Leonetti
  • Matthias Mann

Organizations

  • Chan Zuckerberg Initiative
  • Howard Hughes Medical Institute
  • Jane Coffin Childs Memorial Fund for Medical Research
  • Max Planck Institute of Biochemistry
  • Office of the Director
  • University of California
  • University of Copenhagen

Tags

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Molecular and Cellular Biology

Technology Areas

  • Biotechnology