Andres Ramos group

Molecular recognition in post-transcriptional regulation

Post-transcriptional regulation allows fine tuning of gene expression in complex organisms. Impaired regulatory mechanisms have been linked to cancer, autoimmune and neurodegenerative diseases and viral infection. A molecular understanding of these regulatory mechanisms and of the connection with transcriptional and post-translational regulatory networks is the first step to exploit the potential of protein-RNA regulatory systems in the development of anti-viral and anti-cancer drugs.

Multi-component protein-RNA particles (RNPs) provide a functional connection between the different steps of mRNA metabolism and coordinate post-transcriptional regulation. The assembly of these particles relies on specific protein-protein and protein-RNA recognition events and is regulated both by the action of non-coding RNAs (e.g. miRNAs) and by post-translational modifications (e.g. phosphorylation and methylation) of the proteins involved. Further, recent studies have shown that the protein involved play often a role in itranscriptional regulation, establishing a connection between different steps of gene regulation.

We provide a molecular rationale for protein-protein and protein-RNA recognition within RNPs using a multi-disciplinary approach, applying NMR and other of structural and biophysical techniques (x-ray crystallography, analytical ultracentrifugation, mass spectrometry, circular dichroism, cryoEM etc.) to study these interactions and coordinating our work with in cell/in vivo assays. We are also exploring the the protein-protein and protein-DNA interactions mediated by the same proteins during transcriptional regulation.

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¹⁵N-¹H correlation NMR spectra of KSRP KH3, KH23 and KH34 when bound to Let-7a miRNA TL.

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