Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites

Angela Re; Levi Waldron; Alessandro Quattrone

doi:10.1371/journal.pcbi.1005198

Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites

PLoS Comput Biol. 2016 Dec 6;12(12):e1005198. doi: 10.1371/journal.pcbi.1005198. eCollection 2016 Dec.

Authors

Angela Re¹, Levi Waldron², Alessandro Quattrone¹

Affiliations

¹ Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, Polo Scientifico e Tecnologico Fabio Ferrari, Trento, Italy.
² City University of New York Graduate School of Public Health and Health Policy, New York, New York, United States of America.

Abstract

Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs) and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions from matched transcript and protein datasets. RBPs significantly improved the accuracy in predicting protein abundance of a portion of the total modeled mRNAs in three panels of tissues and cells and for different methods employed in the detection of mRNA and protein. The presence of upstream translation initiation sites (uTISs) at the mRNA 5' untranslated regions was strongly associated with improvement in predictive accuracy. On the basis of these observations, we propose that the recently discovered widespread uTISs in the human genome can be a previously unappreciated substrate of translational control mediated by RBPs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

5' Untranslated Regions / genetics*
Binding Sites / genetics
Computational Biology
Gene Expression Regulation / genetics*
Humans
Models, Genetic*
RNA-Binding Proteins / genetics*
Sequence Analysis, RNA

Substances

5' Untranslated Regions
RNA-Binding Proteins

Grants and funding

The authors received funding for this project from the “Fondazione Caritro Drug Repositioning Scheme” 2016 to the University of Trento. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.