Structural and biophysical mechanism of microRNA nuclear export

Project Information

MICRORNA EXPORT

Grant agreement ID: 220540

Project closed

Start date 12 May 2008

End date 11 May 2010

Funded under

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Total cost € 171 091,96

EU contribution € 171 091,96

Coordinated by

MEDICAL RESEARCH COUNCIL
United Kingdom

Objective

MicroRNAs are a recently discovered class of small non-coding RNAs that act as post-transcriptional regulators of gene expression by silencing target mRNAs. They have wide ranging roles in many cellular processes including cellular proliferation, stress response, apoptosis, development and differentiation. Altered expression of microRNA has been implicated in tumorigenesis, and microRNAs are recognised as modulating factors in numerous cancers including gastric cancer, lung cancer and lymphocytic leukaemia. Specifically, microRNA functions within the cytoplasm in concert with the human-induced silencing complex by binding the 3’ untranslated region of the target mRNA. This binding to target mRNA effectively inhibits expression of the protein, and thus mediates the gene silencing effect of microRNA. This project aims to elucidate the structure and biophysical basis of the nuclear export complex formed by pre-microRNA (precursor of microRNA), RanGTP and exportin-5. These goals will be achieved using a combination of structural, biochemical and biophysical approaches. X-ray crystallography and nuclear magnetic resonance will be utilised to study the structure of the export complex of microRNA. In parallel with the determination of the complex structure, the key residues involved in complex formation will be identified by mutagenesis, cross-linking and further NMR approaches. Furthermore, a range of biophysical techniques will be employed to study the thermodynamic and kinetic basis for the formation of the microRNA export complex. The information provided by this study will be of the highest international standard and will open novel avenues to therapeutic design as well as represent a significant advance in our understanding of cellular biology. Importantly, it will provide a platform for knowledge sharing and collaboration between a European based organization and a top-class non European researcher.

Fields of science

• medical and health sciences › clinical medicine › oncology › lung cancer
• natural sciences › earth and related environmental sciences › geology › mineralogy › crystallography
• natural sciences › biological sciences › biochemistry › biomolecules › proteins
• natural sciences › biological sciences › genetics › RNA
• medical and health sciences › clinical medicine › oncology › leukemia

Keywords

• Cancer
• Crystallography
• MicroRNA
• NMR
• Nuclear Export
• Structural Biology

Programme(s)

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

• PEOPLE-2007-4-2.IIF - Marie Curie Action: "International Incoming Fellowships"

Call for proposal

FP7-PEOPLE-2007-4-2-IIF
See other projects for this call

Funding Scheme

MC-IIF - International Incoming Fellowships (IIF)

Coordinator

MEDICAL RESEARCH COUNCIL

Administrative Contact

Elizabeth Cutler (Ms.)

• EU contribution: € 171 091,96
• Address: 20 Park Crescent ; W1B 1AL LONDON ; United Kingdom
• Activity type: Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
• Total cost: No data