Research Focus
Our laboratory studies different aspects of RNA processing, with a particular emphasis on alternative splicing regulation. We are particularly interested in the trans-acting factors that are involved in the regulation of alternative splicing, such as the SR proteins and hnRNP A/B type of proteins. These proteins have antagonistic activities and their molar ratio influence different modes of alternative splicing in vivo and may represent a mechanism for tissue-specific or developmental regulation of gene expression.
We also study the subcellular distribution of RNA processing factors and how this could be affected by extracellular signals. We have also demonstrated that a subset of SR proteins shuttle continuously from the nucleus to the cytoplasm, and are involved in translational regulation. Thus, shuttling SR proteins play multiple roles in the post-transcriptional expression of eukaryotic genes by coupling splicing and translation.
A combination of different methodologies is used in our research. We mostly rely on classical molecular biology and cellular biology techniques. Cell culture is widely used and we also are using two animal models, mice and the worm C.elegans.
Publications
- Ellis, J.D., Lleres, D., Denegri, M., Lamond, A.I. and Cáceres, J.F. (2008). Spatial mapping of splicing factor complexes involved in exon and intron definition. Journal of Cell Biology 181(6), 921-934.
- Michlewski, G., Sanford, J.R. and Cáceres, J.F. (2008). The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1. Molecular Cell 30, 179-189. Comment/ Reviews on this paper
Bushell, M., Stoneley, M., Spriggs, K.A. and Willis, A.E. (2008). SF2/ASF TORCs Up Translation. Molecular Cell 30, 262-263.
- Guil, S. and Cáceres, J.F. (2007). The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nature Structural & Molecular Biology 14, 591-596.
Comment/ Reviews on this paper
Nielsen, A.F., Leuschner, P.J.F. and Martinez, J. (2007). Not miR-ly a splicing factor: hnRNP A1 succumbs to microRNA temptation. Nature Structural & Molecular Biology 14, 572-573.
- Longman, D., Plasterk, R.H., Johnstone, I.L. and Cáceres, J.F. (2007). Mechanistic insights and identification of two novel factors in the C. elegans NMD pathway. Genes and Development 21,1075-1085.
- Guil, S., Long, J.C., and Caceres, J.F. (2006). hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Molecular and Cellular Biology 26, 5744-5758. PMID: 16847328
- Sanford, J.R., Ellis, J.D., Cazalla, D., and Caceres, J.F. (2005). Reversible phosphorylation differentially affects nuclear and cytoplasmic functions of splicing factor 2/alternative splicing factor. Proceedings of the National Academy of Sciences USA 102, 15042-15047.
- Cazalla, D., Newton, K., and Caceres, J.F. (2005). A Novel SR-Related Protein Is Required for the Second Step of Pre-mRNA Splicing. Molecular and Cellular Biology 25, 2969-2980.
- Sanford, J.R., Gray, N.K., Beckmann, K., and Caceres, J.F. (2004). A novel role for shuttling SR proteins in mRNA translation. Genes and Development 18, 755-768.
- Cazalla, D., Zhu, J., Manche, L., Huber, E., Krainer, A.R., and Caceres, J.F. (2002). Nuclear Export and Retention Signals in the RS Domain of SR Proteins. Molecular and Cellular Biology 22, 6871-6882.
- van Der Houven Van Oordt, W., Diaz-Meco, M.T., Lozano, J., Krainer, A.R., Moscat, J., and Caceres, J.F. (2000). The MKK(3/6)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation. Journal of Cell Biology 149, 307-316.
Key lab techniques: in vitro splicing, in vivo minigene analysis, two-hybrid screening, reporter gene construction, CLIP (UV cross-linking and immunoprecipitation), RNA interference in C.elegans.
Key lab reagents: expression cDNAs for splicing factors, splicing reporters.
Lab contact: Javier Caceres: Javier.Caceres@hgu.mrc.ac.uk
Lab website: http://www.hgu.mrc.ac.uk/Users/Javier.Caceres/
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