A regression-based analysis of ribosome-profiling data reveals a conserved complexity to mammalian translation

Item Type:	Article
Title:	A regression-based analysis of ribosome-profiling data reveals a conserved complexity to mammalian translation
Creators Name:	Fields, A.P. and Rodriguez, E.H. and Jovanovic, M. and Stern-Ginossar, N. and Haas, B.J. and Mertins, P. and Raychowdhury, R. and Hacohen, N. and Carr, S.A. and Ingolia, N.T. and Regev, A. and Weissman, J.S.
Abstract:	A fundamental goal of genomics is to identify the complete set of expressed proteins. Automated annotation strategies rely on assumptions about protein-coding sequences (CDSs), e.g., they are conserved, do not overlap, and exceed a minimum length. However, an increasing number of newly discovered proteins violate these rules. Here we present an experimental and analytical framework, based on ribosome profiling and linear regression, for systematic identification and quantification of translation. Application of this approach to lipopolysaccharide-stimulated mouse dendritic cells and HCMV-infected human fibroblasts identifies thousands of novel CDSs, including micropeptides and variants of known proteins, that bear the hallmarks of canonical translation and exhibit translation levels and dynamics comparable to that of annotated CDSs. Remarkably, many translation events are identified in both mouse and human cells even when the peptide sequence is not conserved. Our work thus reveals an unexpected complexity to mammalian translation suited to provide both conserved regulatory or protein-based functions.
Keywords:	Amino Acid Sequence, Conserved Sequence, Cultured Cells, Dendritic Cells, Lipopolysaccharides, Open Reading Frames, Proteome, Proteomics, Regression Analysis, Ribosomes, Animals, Mice
Source:	Molecular Cell
ISSN:	1097-2765
Publisher:	Cell Press
Volume:	60
Number:	5
Page Range:	816-827
Date:	3 December 2015
Official Publication:	https://doi.org/10.1016/j.molcel.2015.11.013
PubMed:	View item in PubMed

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