title: ceRNA crosstalk stabilizes protein expression and affects the correlation pattern of interacting proteins.
abstract: Gene expression is a noisy process and several mechanisms, both transcriptional and post-transcriptional, can stabilize protein levels in cells. Much work has focused on the role of miRNAs, showing in particular that miRNA-mediated regulation can buffer expression noise for lowly expressed genes. Here, using in silico simulations and mathematical modeling, we demonstrate that miRNAs can exert a much broader influence on protein levels by orchestrating competition-induced crosstalk between mRNAs. Most notably, we find that miRNA-mediated cross-talk (i) can stabilize protein levels across the full range of gene expression rates, and (ii) modifies the correlation pattern of co-regulated interacting proteins, changing the sign of correlations from negative to positive. The latter feature may constitute a potentially robust signature of the existence of RNA crosstalk induced by endogenous competition for miRNAs in standard cellular conditions.
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.
authors.forename: Araks
authors.initials: A
authors.lastname: Martirosyan
authors.affiliation: Soft &Living Matter Lab, Istituto di Nanotecnologia (NANOTEC-CNR), Rome, Italy.|Human Genetics Foundation, Turin, Italy.|Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Martino
authors.affiliation: Human Genetics Foundation, Turin, Italy.|Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pagnani
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.|INFN, Sezione di Roma 1, Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Marinari
mesh_terms: D000465:Algorithms; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D011485:Protein Binding; D055550:Protein Stability; D012313:RNA / Q000235:genetics*; D034622:RNA Interference; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D035683:MicroRNAs; D012313:RNA