MRC Laboratory of Molecular Biology

  • Increase font size
  • Default font size
  • Decrease font size
Home Group Leaders N to S Lori Passmore
Lori Passmore

Macromolecular machines involved in mRNA polyadenylation

Wiederhold K, Passmore LA. (2010)
Cytoplasmic deadenylation: regulation of mRNA fate.
Biochem. Soc. Trans. 38(6):1531-6

Passmore L.A., Schmeing T.M., Maag D., Applefield D.J., Acker M.G., Algire M.A., Lorsch J.R. & Ramakrishnan V.(2007)
The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome.
Mol. Cell 26, 41-50.

Passmore L.A., Booth C.R., Venien-Bryan C., Ludtke S.J., Fioretto C., Johnson L.N., Chiu W. & Barford D. (2005)
Structural analysis of the anaphase-promoting complex reveals multiple active sites and insights into polyubiquitylation.
Mol. Cell 20, 855-866.

 

Visit my group page here

Contact me by email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Group Members

  • Katrin Wiederhold
  • Eeson Rajendra
  • Ashley Easter
  • Jana Wolf
  • Chris Russo
Eukaryotic genes are normally transcribed as pre-mRNAs that must be processed before they are exported from the nucleus and translated into proteins. The pre-mRNA is cleaved and a poly(A) tail is added to its 3' end. Several protein factors are required to coordinate the 3´ end-processing reactions, including a large multiprotein complex called Cleavage and Polyadenylation Factor (CPF).

 

The poly(A) tail is required for export of the mRNA into the cytoplasm, to enhance mRNA stability and to stimulate translation. Its length can be regulated to influence these functions. For example, shortening of thepoly(A) tail can decrease the efficiency of translation to control gene expression, and is the first step in mRNA turnover. The main deadenylase activity in yeast is found within the evolutionarily conserved, 1MDa Ccr4-Not complex.

We are using a hybrid approach to understand the molecular mechanisms of CPF and Ccr4-Not. In particular, we use cryo-electron microscopy (cryo-EM), alongside x-ray crystallographic, biophysical, biochemical and genetic techniques. Our aim is to establish fundamental principles underlying the assembly of multi-protein complexes, define their structures, gain insight into their activities and regulation, and identify roles for proteins of unknown function.

 

Last Updated on Friday, 15 July 2011 08:34