A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation
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Regev_A regression-based.pdf
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Author(s)
Fields, Alexander P.
Rodriguez, Edwin H.
Jovanovic, Marko
Stern-Ginossar, Noam
Haas, Brian J.
Mertins, Philipp
Raychowdhury, Raktima
Hacohen, Nir
Carr, Steven A.
Ingolia, Nicholas T.
Date Issued
December 2015
Journal
Molecular Cell
Publisher
Elsevier
Citation
Fields, Alexander P. et al. “A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation.” Molecular Cell 60.5 (2015): 816–827.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2015.11.013
