MRC National Institute for Medical Research, London
Science for Health
Andres Ramos group project:
Regulation of mRNA metabolism - ARE mediated mRNA degradation
Adenine-uracil-rich element (ARE)-mediated mRNA decay (AMD) regulates the concentration of a class of mRNAs that contain AU-rich sequences within their 3′ untranslated regions (3′UTRs). The AMD-regulated genes are involved in cellular proliferation, immune response and cardiovascular toning. Impaired AMD results in cancer insurgence and progression and is linked to inflammatory diseases such as Crohn-like inflammatory bowel disease and inflammatory arthritis.
ARE-binding proteins (ABPs) recruit the cytoplasmic mRNA degradation machinery to the target mRNAs leading to their 3′-to-5′ degradation (See figure). ABP recognition of specific AREs provides therefore the selectivity of the degradation mechanism. The K-homology splicing regulator protein (KSRP) is a multi-domain protein that has been used as a functional model for AMD (Gherzi et al, 2004). We investigate how KSRP uses different combinations of its four RNA-binding domains to recognise selectively its targets and how protein-protein interactions modulate KSRP-RNA recognition and KSRP function (García-Mayoral et al, 2008, García-Mayoral et al, 2007).
ARE mediated mRNA degradation
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KSRP recruits the exosome and PARN to the target mRNAs leading to 3′-to-5′ degradation.
Selected publications
- 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 - García-Mayoral, MF., Hollingworth, D., Masino, L., Díaz-Moreno, I., Kelly, G., Gherzi, R., Chou, C-F., Cheng, C-Y and Ramos A. (2007)
The structure of the C-terminal domains of KSRP reveal a new element important to mRNA degradation
Structure 15, 485-498 PubMed abstract
Ramos group
Recent publications
Research projects
- Regulation of miRNA biogenesis
- Regulation of mRNA metabolism - ARE mediated mRNA degradation
- Integration of mRNA metabolism and signalling pathways
- Methods to study protein-RNA interactions
Ramos biography
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