Ramos group

Research overview

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.

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.

We want to provide a molecular rationale for protein-protein and protein-RNA recognition within RNPs and understand the regulation of RNPs activity. To achieve such understanding we require a multi-disciplinary approach that makes use of structural and biophysical techniques (NMR, x-ray crystallography, analytical ultracentrifugation, mass spectrometry, circular dichroism, cryoEM etc.) as well as of in cell/in vivo assays. NMR plays an important role because of both its capability to observe flexible systems and its capability to coordinate information on structure, dynamics and interactions.

Our molecular work on mRNA metabolism is the first step to exploit the potential of protein-RNA regulatory systems in the development of anti-viral and anti-cancer drugs.

Selected publications

• Trabucchi, M; Briata, P; Garcia-Mayoral, M; Haase, AD; Filipowicz, W; Ramos, A; Gherzi, R and Rosenfeld, MG (2009)
  The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs.
  Nature 459, 1010-1014 PubMed abstract
• Díaz-Moreno, I; Hollingworth, D; Frenkiel, TA; Kelly, G; Martin, S; Howell, S; García-Mayoral, M; Gherzi, R; Briata, P and Ramos, A (2009)
  Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding.
  Nature Structural & Molecular Biology 16, 238-246 PubMed abstract
• García-Mayoral, MF; Díaz-Moreno, I; Hollingworth, D and Ramos, A (2008)
  The sequence selectivity of KSRP explains its flexibility in the recognition of the RNA targets.
  Nucleic Acids Research 36, 5290-5296 PubMed abstract
• Beuth, B; García-Mayoral, MF; Taylor, IA and Ramos, A (2007)
  Scaffold-independent analysis of RNA-protein interactions: The Nova-1 KH3-RNA complex.
  Journal of the American Chemical Society 129, 10205-10 PubMed abstract
• García-Mayoral, MF; Hollingworth, D; Masino, L; Díaz-Moreno, I; Kelly, G; Gherzi, R; Chou, C-F; Chen, C-Y and Ramos, A (2007)
  The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation.
  Structure 15, 485-498 PubMed abstract
• Hollingworth, D; Noble, CG; Taylor, IA and Ramos, A (2006)
  RNA polymerase II CTD phosphopeptides compete with RNA for the interaction with Pcf11.
  RNA 12, 555-60 PubMed abstract
• Noble, CG; Hollingworth, D; Martin, SR; Ennis-Adeniran, V; Smerdon, SJ; Kelly, G; Taylor, IA and Ramos, A (2005)
  Key features of the interaction between Pcf11 CID and RNA polymerase II CTD.
  Nature Structural & Molecular Biology 12, 144-51 PubMed abstract

[Page last updated August 2009]