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Prof Andres Ramos
Professor of RNA Biology
Structural & Molecular Biology
Div of Biosciences
- Joined UCL
- 21st Aug 2009
Research summary
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.
Teaching summary
Andres Ramos is responsible for two lecture series. In the first (module BIOC1007) he teaches on on the methods to study the structure, dynamics and interactions of macromolecules and macromolecular assemblies. In the second (module BIOC3024) he teaches on RNA biology and in particular on the biogenesis, function and networks of miRNAs, on mRNA transport and localised translation and on mRNA decay pathways. Further, he teaches on the assembly and regulation of the RNA polymerase II complex (module BIOC3014).
Biography
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