AddressRNA regulation laboratory, 514a
Research Department of Structural & Molecular Biology
Darwin Building, Gower St
Professor of RNA Biology
Structural & Molecular Biology
Div of Biosciences
The regulation of mRNA metabolism, transport and translation expands genomic diversity and provides a layer of control of gene expression essential for the development of complex organisms.
A key area of research in our group is the regulation of mRNA transport and local translation in neuronal development and function. Establishing and maintaining the complex network of connections required for neuronal communication requires the regulated transport of hundreds to thousands of mRNAs to specific locations in the cell and their in situ translation. RNA-binding proteins mediate the interaction of the mRNAs with the machines of cellular transport, as well as the regulation of the mRNAs’ translation control. We use a combination of newly designed and established structural and biophysical methods in combination with cell-biology tools to describe the protein-protein and protein-RNA interactions and build mechanistic models for this regulation. Importantly, mis-function or mis-expression of the proteins regulating local mRNA translation in neurons is at the basis of neuro-developmental and neuro-degenerative disorders. A molecular understanding of the regulatory pathways is key to exploit the potential of mRNA local translation in diagnosis and therapy.
A second area of research is the regulation of miRNA biogenesis and transport. miRNAs are short, single-stranded RNA molecules that direct silencing complexes to the target mRNAs. miRNA-mediated regulation confer robustness to gene expression programs in development and in cell differentiation. The complex biogenesis of miRNAs is regulated by a number of RNA-binding proteins and we use the inter-disciplinary strategy outlined above to define how these proteins regulate miRNA biogenesis and how the mature miRNAs are transported to mediate inter-cellular communication. Understanding the mechanisms underlying miRNA biogenesis and transport provides an entry point to manipulate the miRNAs concentration and their loading into delivery vessels.
Andres Ramos has a PhD from
Selected research papers:
Hobor, F., Dallmann, A., Ball, N. J., Cicchini, C., Battistelli, C., Ogrodowicz, R. W., . . . Ramos, A.* (2018). A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets. Nature communications, 9 (1), 831.
Nicastro, G., Candel, A. M., Uhl, M., Oregioni, A., Hollingworth, D., Backofen, R., . . . Ramos, A.* (2017). Mechanism of β-actin mRNA Recognition by ZBP1. Cell Rep., 18 (5), 1187-1199.
Collins, K., Oregioni, A., Robertson L.E., Kelly, G., and Ramos, A.* (2015). Protein-RNA specificity by high-throughput principal component analysis of NMR spectra. Nucleic Acid Res. doi:10.1093/nar/gku1372
Nicastro, G., García-Mayoral, MF., Hollingworth, D., Kelly, G., Martin, S.R., Briata, P., Gherzi, R. and Ramos, A.* (2012). Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis. Nat. Struct. Mol. Biol. 19, 1282-1286. PMID:23142982
Cukier, C.D., Hollingworth, D., Kelly, G., Martin, S.R., Díaz-Moreno, I., and Ramos, A.* (2010). Molecular basis of FIR-mediated c-myc transcriptional control. Nat. Struct. Mol. Biol. 17, 1058-1064. PMID:20711187
Díaz-Moreno, I., Hollingworth, D., Frenkiel, T.A., Kelly, G., Martin, S.R., Howell, S., García-Mayoral, MF., Gherzi., R., Briata P. and Ramos, A.* (2009). Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding. Nat. Struct. Mol. Biol. 16, 238-246. PMID:19198587
Trabucchi, M., Briata, P., Garcia-Mayoral, MF., Haase A., Filipowicz, W ., Ramos, A.*, Gherzi, R. and Rosenfeld, G.M. (2009). The RNA binding protein KSRP promotes the biogenesis of a subset of miRNAs. Nature 459, 1010-1014. PMID:19458619
Beuth, B., Garcia-Mayoral, MF., Taylor, I.A. and Ramos, A.* (2007). Scaffold Independent Analysis of RNA-protein interactions: the Nova-1 KH3-RNA complex. J. Am. Chem. Soc., 129, 10205-10210. PMID:17655233
* Corresponding author