title: Silent Polymorphisms: Can the tRNA Population Explain Changes in Protein Properties?
abstract: Silent mutations are being intensively studied. We previously showed that the estrogen receptor alpha Ala87's synonymous polymorphism affects its functional properties. Whereas a link has been clearly established between the effect of silent mutations, tRNA abundance and protein folding in prokaryotes, this connection remains controversial in eukaryotic systems. Although a synonymous polymorphism can affect mRNA structure or the interaction with specific ligands, it seems that the relative frequencies of isoacceptor tRNAs could play a key role in the protein-folding process, possibly through modulation of translation kinetics. Conformational changes could be subtle but enough to cause alterations in solubility, proteolysis profiles, functional parameters or intracellular targeting. Interestingly, recent advances describe dramatic changes in the tRNA population associated with proliferation, differentiation or response to chemical, physical or biological stress. In addition, several reports reveal changes in tRNAs' posttranscriptional modifications in different physiological or pathological conditions. In consequence, since changes in the cell state imply quantitative and/or qualitative changes in the tRNA pool, they could increase the likelihood of protein conformational variants, related to a particular codon usage during translation, with consequences of diverse significance. These observations emphasize the importance of genetic code flexibility in the co-translational protein-folding process.
authors.affiliation: Biochemistry-Molecular Biology, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. tamfer@pasteur.edu.uy.|Bioinformatics Unit, Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. tamfer@pasteur.edu.uy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Calero
authors.affiliation: Biochemistry-Molecular Biology, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. florenciacabreracabrera@gmail.com.
authors.forename: Florencia
authors.initials: F
authors.lastname: Cabrera-Cabrera
authors.affiliation: Biochemistry-Molecular Biology, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. ehrlich@fcien.edu.uy.|Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. ehrlich@fcien.edu.uy.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ehrlich
authors.affiliation: Biochemistry-Molecular Biology, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. marin@fcien.edu.uy.
authors.forename: Mónica
authors.initials: M
authors.lastname: Marín
keywords: estrogen receptor alpha; isoacceptor tRNAs; protein folding; synonymous polymorphisms; translation kinetics