Award details

Cytoplasmic polyadenylation in NIH3T3 cells

Reference	BB/G001847/1
Principal Investigator / Supervisor	Dr Cornelia Huiberdina de Moor
Co-Investigators / Co-Supervisors
Institution	University of Nottingham
Department	Sch of Pharmacy
Funding type	Research
Value (£)	528,671
Status	Completed
Type	Research Grant
Start date	01/12/2008
End date	30/11/2011
Duration	36 months

Abstract

The poly(A) tail of an mRNA is plays an important role in its translation and stability, and its regulation is therefore a major determinant of gene expression. Most mRNAs receive long poly(A) tails in the nucleus, which become shorter and more heterogeneous upon entry in the cytoplasm through the action of general or mRNA specific deadenylase complexes. In addition, elongation of the poly(A) tail also takes place in the cytoplasm in mammalian tissue culture cells, accounting for approximately 10% of all polyadenylation. This indicates that a combination of shortening and lengthening determines poly(A) tail length of a significant percentage of mRNAs in the cytoplasm. Regulation by cytoplasmic polyadenylation of specific mRNAs has been extensively studied in oocyte maturation, where it is a crucial regulatory mechanism, and has also been repeatedly demonstrated to play a role in synaptic plasticity in neurons. However, it is unclear whether cytoplasmic polyadenylation also regulates specific mRNAs in other cell types. We investigated cytoplasmic polyadenylation in cell adhesion because there were multiple reports in the literature that this important process is regulated post-transcriptionally. We have now proven that cytoplasmic polyadenylation plays a role in cell adhesion and that specific mRNAs are polyadenylated during this process. In this project, we will characterise the cytoplasmic polyadenylation substrate mRNAs and the cytoplasmic polyadenylation machinery in these cells in more detail. In this project we aim to: 1. Identify further mRNAs that are regulated by cytoplasmic polyadenylation during suspension and adhesion of NIH 3T3 cells 2. Study the translational activity and stability of these mRNAs during cytoplasmic polyadenylation 3. Characterise the cytoplasmic polyadenylation sequences in these mRNAs 4. Identify the RNA binding factors and poly(A) polymerase(s) involved

Summary

Regulation of gene expression determines the level of specific proteins in a cell and can be controlled in many ways to allow processes such as growth and the prevention of disease. Cytoplasmic polyadenylation is a form of this regulation by which the production of protein from an mRNA can be controlled. It is very important in eggs and has also been detected in the brain. However it is not clear whether it plays a role in any other types of cells. We have recently shown that cytoplasmic polyadenylation also occurs when fibroblasts attach to a new surface. Fibroblasts are skin cells and their attachement contributes to skin healing. Fibroblasts are much less specialised than eggs or brain cells, indicating that regulation by cytoplasmic polyadenylation may be a general phenomenon. We are now planning to investigate how widespread cytoplasmic polyadenylation is in fibroblasts and what proteins are required for this process. The data gathered in this project will ultimately have relevance for many medical problems, such as wound healing and the spreading of cancer cells through the body.

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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