title: Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites.
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.
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, Polo Scientifico e Tecnologico Fabio Ferrari, Trento, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Re
authors.affiliation: City University of New York Graduate School of Public Health and Health Policy, New York, New York, United States of America.
authors.forename: Levi
authors.initials: L
authors.lastname: Waldron
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, Polo Scientifico e Tecnologico Fabio Ferrari, Trento, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D020121:5' Untranslated Regions; D016601:RNA-Binding Proteins