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Translational control of virus gene expression through protein-stimulated ribosomal frameshifting

Translational control of virus gene expression through protein-stimulated ribosomal frameshifting

Based at Division of Virology, Addenbrooke’s Hospital
Supervised by Dr Ian Brierley

Background

Translational control of virus gene expression is widespread and varied. We study programmed ribosomal frameshifting (PRF), a process in which ribosomes translating an mRNA change reading frame in response to an mRNA signal and continue translating an overlapping coding sequence. It is especially exploited by RNA viruses in the regulated expression of viral replicases. PRF requires the action of a stimulatory RNA structure that modulates ribosome function. Recently, we identified the first examples of PRF where the action of a trans-acting protein factor is required. This project will study protein-mediated PRF in viruses using molecular virology and structural biology approaches.

Recent Publications:

Strnadova P, Ren H, Valentine R, Mazzon M, Sweeney TR, Brierley I and Smith GL. Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus Virulence. PLoS Pathog. 11:e1005151.

 

Chung BY, Hardcastle TJ, Jones JD, Irigoyen N, Firth AE, Baulcombe DC and Brierley I (2015) The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis. RNA 21:1731-1745.

 

Finch LK, Ling R, Napthine S, Olspert A, Michiels T, Lardinois C, Bell S, Loughran G, Brierley I and Firth AE (2015) Characterization of ribosomal frameshifting in Theiler's murine encephalomyelitis virus. J. Virol. 89:8580-8589.

 

Csibra E, Brierley I, Irigoyen N. (2014). Modulation of stop codon read-through efficiency and its effect on the replication of murine leukemia virus. J. Virol. 88:10364-10376.

 

Li Y, Treffers EE, Napthine S, Tas A, Zhu L, Sun Z, Bell S, Mark BL, van Veelen PA, van Hemert MJ, Firth AE, Brierley I, Snijder EJ & Fang Y. (2014). Transactivation of programmed ribosomal frameshifting by a viral protein. Proc. Natl. Acad. Sci. U.S.A. 111:E2172-2181.

 

More information on the supervisor’s research can be found on their research group website

http://www.path.cam.ac.uk/directory/ian-brierley