Structure and function of multi-protein complexes that regulate mRNA poly(A) tails
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Gene expression is tightly controlled to allow rapid responses to cellular stimuli.It is regulated through transcription, translation and mRNA stability. Its deregulation is associated with human diseases (e.g. cancer).
Poly(A) tails are found on almost all eukaryotic mRNAs. They play important roles in mRNA stability, are required for export of mRNA from the nucleus and regulate the efficiency of translation. Thus, control of poly(A) tail length can be used to fine-tune protein synthesis, for example during development. Although the proteins that add and remove poly(A) tails are known, their mechanisms are poorly understood.
We are interested in understanding how macromolecular machines contribute to the regulation of gene expression. Specifically, we are investigating the multi-protein complexes that add or remove poly(A) tails on mRNAs. We aim to understand how these complexes are regulated, how they recognise mRNA, and the specific roles of subunits.
I am looking for a motivated and enthusiastic student to join the group. A wide range of techniques are employed by the group, including cryo-electron microscopy (cryo-EM), x-ray crystallography, genetics, biophysics and biochemical assays.
Please see my website for more information.
Casañal A, Kumar A, Hill CH, Easter AD, Emsley P, Degliesposti G, Gordiyenko Y, Santhanam B, Wolf J, Wiederhold K, Dornan GL, Skehel M, Robinson CV and Passmore LA (2017)
Architecture of eukaryotic mRNA 3′-end processing machinery
Science 348: 1056-1059
Webster MW, Chen YH, Stowell JAW, Alhusaini N, Sweet T, Graveley BR, Coller J, Passmore LA (2018)
mRNA Deadenylation Is Coupled to Translation Rates by the Differential Activities of Ccr4-Not Nucleases.
Mol Cell 70(6):1089-1100.
Stowell JA, Webster MW, Kögel A, Wolf J, Shelley K, Passmore LA (2016)
Reconstitution of Targeted Deadenylation by the Ccr4-Not Complex and the YTH Domain Protein Mmi1
Cell Reports 17(8):1978-1989.
Russo CJ, Passmore LA. (2014)
Ultra stable gold substrates for electron cryomicroscopy.