Research Groups

RNA Biology

Research Interests and Description

Group Leader: Francisco E. Baralle, MD PhD

Group Members

Research Interests

Genetic diseases caused by defective splicing, RNA splicing mechanisms, RNA metabolism in physiological and pathological neural function

Description of Research

Our Group is currently investigating a mutually exclusive splicing event described to occur in two neuronal sodium channels, SCN8A (Nav 1.6) and SCN9A. These studies have uncovered the complex network of RNA-protein interactions that determine exon inclusion according to specific cell types. Particularly interesting is the role played in this process by neural specific factor such as the Fox protein family and ubiquitous factors of the likes of SR proteins and hnRNPs whose levels vary during neural development. These results will hopefully pave the way for a clinical evaluation of the most successful effectors that can be used to modify aberrant regulation in a human setting.

In parallel, we have continued our characterization of the molecular mechanisms that control (and are controlled by) the TDP-43 protein, initially identified as an hnRNP by our laboratory in 2001. In particular, the RNA Biology group focuses in the self-regulation mechanism through which TDP 43 controls its cellular levels. In previous reports, we have shown the importance of several cis-acting elements (S.E. Avendaño-Vázquez, Genes Dev. (2012) and S. Bembich, Nucleic Acids Res. (2014)).  Currently, our research is aimed at elucidating the role of the poly A sites structure and configuration around the splice site in the self regulation mechanism. In addition, there are close collaborations with the Molecular Pathology, Neurobiology and Biotechnology Development groups to assess the impact of TDP 43 dysfunction in cellular and animal models and their possible modulation by agents that can have a potential therapeutic use. 

Recent Publications

Baralle, F.E., Giudice, J. 2017. Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol 18, 437-451 PubMed link

Mompeán, M., Romano, V., Pantoja-Uceda, D., Stuani, C., Baralle, F.E., Buratti, E., Laurents, D.V. 2017. Point mutations in transactive response DNA-binding protein 43 (TDP-43)'s N-terminal domain compromise its stability, dimerization and functions. J Biol Chemjbc.M117.775965. doi: 10.1074/jbc.M117.775965. [Epub ahead of print] PubMed link

Langellotti, S., Romano, V., Romano, G., Klima, R., Feiguin, F., Cragnaz, L., Romano, M., Baralle, F.E. 2016. A novel Drosophila model of TDP-43 proteinopathies: N-terminal sequences combined with the Q/N domain induce protein functional loss and locomotion defects. Dis Model Mech 9, 659-669 PubMed link

Budini, M., Romano, V., Quadri, Z., Buratti, E., Baralle, F.E. 2015. TDP-43 loss of cellular function through aggregation requires additional structural determinants beyond its C terminal Q/N prion-like domain. Hum Mol Genet 24, 9-20 PubMed link

Cragnaz, L., Klima, R., Skoko, N., Budini, M., Feiguin, F., Baralle, F.E. 2014. Aggregate formation prevents dTDP-43 neurotoxicity in the Drosophila melanogaster eye. Neurobiol Dis 71C, 74-80 PubMed link

Romano, G., Klima, R., Buratti, E., Verstreken, P., Baralle, F.E., Feiguin, F. 2014.Chronological requirements of TDP-43 function in synaptic organization and locomotive control. Neurobiol Dis 71C, 95-109[nbsp]PubMed link

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