Structure of the TDP43 (green) – RNA (yellow) complex, Lukavsky et al, Nature Structural and Molecular Biology (2013)
Alternative splicing is a process allowing cells to make different products from one gene. Since it was discovered over three decades ago now, it has been shown that it has key roles especially in tissue differentiation and pathologies like hereditary diseases and cancer.
Frédéric Allain is determining with his team the structure of protein/RNA complexes involved in alternative splicing by nuclear magnetic resonance spectroscopy.
Almost 20% of genetic diseases originate from a post-transcriptionnal misregulation of gene expression that is often correlated with errors in pre-mRNA alternative splicing and/or RNA editing.
Alternatively-spliced and edited mRNAs are particularly abundant in the neurons. The finely regulated proportions of the different isoforms of most neurotransmitter receptors, ion channels, neuronal cell surface receptors and adhesion molecules ensure a proper brain function. Several neuron-associated diseases such as FTDP (Frontotemporal Dementia with Parkinsonism) or SMA (Spinal Muscular Atrophy) originate from a single nucleotide mutation in the pre-mRNA resulting in an imbalanced ratio between alternatively-spliced protein variants. The mutations are located in an alternatively-spliced exon and are speculated to weaken critical interactions with a protein splicing factor.
The knowledge of parameters involved in these misregulations at the molecular level can help understanding these diseases and finding out new ways of treatment. Frédéric Allain and his lab are focusing on determining the structures at atomic resolution of such Protein-RNA-complexes using Nuclear Magnetic Resonance spectroscopy (NMR).
• 1996 Ph. D. Cambridge University, United Kingdom, Gabriele Varani's lab
• 1997-2000 Post-doctoral fellow, University of California Los Angeles, USA, Juli Feigon's lab
• 2000-2001 Research Associate, HHMI, University of California Los Angeles, USA, Doug Black’s lab
• 2001 Appointed Assistant Professor and Group Leader, ETH, Zürich, Switzerland
• Elected EMBO Member, 2009
• Young Investigator Award, EMBO, 2003
• Boyer-Parvin postdoctoral recognition award, MBI-UCLA, 2000
• Chancellor award for Postdoctoral research, UCLA, 2000
• Max Perutz Student Prize, LMB-MRC, 1996
Mar 2014, Nat. Struct. Mol. Biol.
Dec 2013, Nat. Struct. Mol. Biol.