Glauco P. Tocchini-Valentini

Clincians

Research Focus

We are studying cis-and trans- nonspliceosomal splicing catalysed by an archaeal endonuclease in mouse cells and in mice. The tRNA endonuclease from Methanococcus jannaschij (MJ endonuclease) can cleave RNAs forming specific bulge-helix-bulge (BHB) structures recognised by the enzyme. The resulting products are subsequently joined together by an endogenous ligase. The only requirement of the archaeal endonuclease is a BHB in its substrate RNAs, that is, a structure rather than a specific sequence; this allows great freedom in creating and presenting diverse targets in mRNA as well as other RNAs.

The MJ endonucleases is an homotetramer; other archaeal tRNA endonucleases, presenting different architectures, are available. Induced trans-splicing results in the production of fusion-proteins. We are using this emergent technology (Archaeaexpress) to introduce perturbations at the RNA level. Archaeaexpress parallels and complements Cre-lox technology. We are particularly interested in applying Archaeaexpress to dopaminergic neurons that are involved in Parkinson's disease.

Publications

Di Segni, G., Gastaldi, S., Tocchini-Valentini, G.P. (2007). Cis- and trans-splicing of mRNAs mediated by tRNA sequences in eukaryotic cells. Proceedings of the National Academy of Sciences USA 2008 May 5. [Epub ahead of print]
Marazziti, D., Mandillo, S., Di Pietro, C., Golini, E., Matteoni, R., Tocchini-Valentini, G.P. (2007). GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs. Proceedings of the National Academy of Sciences USA 104(23), 9846-51. PMID: 17519329 [PubMed - indexed for MEDLINE]
Tocchini-Valentini, G. D., Fruscoloni, P. and Tocchini-Valentini, G.P.(2007). The dawn of dominance by the mature domain in tRNA splicing. Proceedings of the National Academy of Sciences 104, 12300-12305.
Di Segni, G., Borghese, L., Sebastiani, S. and Tocchini-Valentini, G.P. (2005). A pretRNA carrying intron features typical of Archaea is pliced in yeast. RNA 11, 70-76.
Tocchini-Valentini, G. D., Fruscoloni, P. and Tocchini-Valentini, G.P. (2005). Structure, function, and evolution of the tRNA endonucleases of Archaea: an example of subfunctionalization. Proceedings of the National Academy of Sciences 102, 8933-8938.
Tocchini-Valentini, G. D., Fruscoloni, P. and Tocchini-Valentini, G.P.(2005). Coevolution of tRNA intron motifs and tRNA endonuclease architecture in Archaea. Proceedings of the National Academy of Sciences 102, 15418-15422.
Deidda, G., Rossi, N. and Tocchini-Valentini, G.P. (2003). An archaeal endoribonuclease catalyses cis- and trans- non-spliceosomal splicing in murine cells. Nature Biotechnology 21, 1499-1504.
Fabbri, S., Fruscoloni, P., Bufardeci, E., Di Nicola Negri, E., Baldi, M.I., Gandini Attardi, D., Mattoccia, E., Tocchini-Valentini, G.P. (1998). Conservation of substrate recognition mechanisms by tRNA splicing endonucleases. Science 280(5361), 284-6.