Research Biographies

back to contents

DR JAVIER CACERES

Chromosomes and Gene Expression

Programme Leader


Javier Caceres

Contact Details

E-mail address: j.caceres@hgu.mrc.ac.uk
Telephone: +44 (0)131 332 2471 (extension 2301)
Fax: +44 (0)131 467 8456
Address: Medical Research Council
Human Genetics Unit
Western General Hospital
Crewe Road
Edinburgh EH4 2XU
Research Programme: RNA Processing in Eukaryotes

 

 

Research Areas

 RNA Processing in Eukaryotes

Gene expression is extensively regulated at the post-transcriptional level. The fundamental steps of eukaryotic RNA processing have been characterised in great detail, but knowledge of how the disruption of these processes contributes to human disease has only recently begun to emerge. The major aim of this programme is to study the mechanisms for the post-transcriptional regulation of gene expression. Our laboratory studies different aspects of RNA processing, including alternative splicing regulation, nonsense-mediated decay (NMD) and microRNA (miRNA) processing.

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. More recently, we have uncovered functions for splicing factors in the regulation of translation.

MicroRNAs are small non-coding RNA gene products of approximately 22 nucleotides in length that negatively regulate the expression of complementary messenger RNAs. We have also recently found that hnRNP A1, a general RNA binding protein that has been implicated in various roles in RNA metabolism, has a function in miRNA biogenesis. This suggests the existence of auxiliary factors for miRNA processing and raises the exciting possibility of being able to manipulate miRNA production and function.


Recent Publications

  • Biamonti, G. and Caceres, J.F. Cellular stress and RNA splicing. Trends in Biochem Sci 34(3):146-53, 2009 PubMed Abstract
  • Long, J.C. and Caceres, J.F. The SR protein family of splicing factors: master regulators of gene expression. Biochem J 417(1):15-27, 2009 PubMed Abstract
  • Macias, S.; Michlewski, G. and Caceres, J.F. Hormonal Regulation of MicroRNA Biogenesis.
    Molecular Cell     36:172-173, 2009 PubMed Abstract
  • Ellis, J.D.; Lleres, D.; Denegri, M.; Lamond, A.I. and Caceres, J.F. Spatial mapping of splicing factor complexes involved in exon and intron definition. Journal of Cell Biology 181(6):921-934, 2008 PubMed Abstract
  • Michlewski, G.; Guil, S.; Semple, C. and Caceres, J.F. Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Molecular Cell 32(3):383-393, 2008 PubMed Abstract
  • Michlewski, G.; Sanford, J.R. and Caceres, J.F. The Splicing Factor SF2/ASF regulates translation initiation of cellular mRNAs by enhancing phosphorylation of 4EBP. Molecular Cell 30(3):179-189, 2008 PubMed Abstract
    Comment/ Reviews on this paper Bushell,M.; Stoneley,M.; Spriggs, K.A. and Willis,A.E. SF2/ASF TORCs Up Translation. Mol Cell     30:262-263, 2008 PubMed Abstract
  • Sanford, J.R.; Coutinho, P.; Hacket, J.A.; Wang, X.; Ranahan, W. and Caceres, J.F. Identification of nuclear and cytoplasmic mRNA targets for the shuttling protein SF2/ASF. PLoS ONE 3(10): e3369, 2008 PubMed Abstract