Professor John F. Atkins
Codes with THE code. Signals buried within the coding sequence of a minority of mRNAs in probably all organisms stimulate a non-standard decoding event utilized for gene expression purposes. The non-standard event can be local redefinition of codon meaning, a shift of reading register or the bypassing of a block of nucleotides present in the mature mRNA. The efficiency of some of the "recoding" events is responsive to the cellular level of a component, such as polyamines or release factor 2, and these events can serve an autoregulatory function. In others there is a fixed ratio of the product of standard decoding to that of the recoding product which serves some unique function.
We are investigating the occurrence, mechanisms involved and the functions of recoding. In addition to seeking basic understanding, we are also using the potential to manipulate recoding and related aspects of protein synthesis for societal beneficial purposes. In that regards we are seeking small molecule inhibitors of Foot and Mouth Disease propagation via targeting an unusual form of recoding required for viral expression but is not utilized by viral hosts.
In 2012 together with collaborators elsewhere we discovered that the pig pathogen Porcine Reproductive and Respiratory Syndrome Virus and other arteriviruses utilize a different form of recoding, programmed -2 frameshifting, that is a potentially useful antiviral target and are searching for other novel recoding-based targets.
We are also investigating the nature of the recoding required for synthesis in mammals of the selenium transport protein and starting to employ the reagents being generated for clinical purposes. We are keen to exploit knowledge gained from recoding and related studies for the amelioration of genetic disease, to optimize protein synthesis under particular over-expression situations.
Current group members
Research Fellow and Lab Manager
Past Lab Members
Ming-Yuan Chou (Brno, Czech Republic)
Martin Mullins, Vice President, Whitehead Institute, affiliated with MIT
Daniel J. O’Mahony, Partner, Seroba Kernel Life Science (biotech venture capital) Molesworth Street, Dublin 2.
Full list of publications
For publications 1995 to date, please visit John F. Atkins publications on PubMed.
Selected publications 2008 -2014
RNA worlds: From life’s origins to diversity in gene regulation.
Atkins, J. F., Gesteland, R. F., & Cech, T. (Eds.). (2011).
New York;: Cold Spring Harbor Laboratory Press.
Recoding: Expansion of Decoding rules enriches gene expression.
J.F. Atkins and R.F. Gesteland. (2010).
New York: Springer Science+Business Media, LLC.
An overlapping protein-coding region in influenza A virus segment 3 modulates the host response.
Jagger, B. W., H. M. Wise, J. C. Kash, K. A. Walters, N. M. Wills, Y. L. Xiao, R. L. Dunfee, L. M. Schwartzman, A. Ozinsky, G. L. Bell, R. M. Dalton, A. Lo, S. Efstathiou, J. F. Atkins, A. E. Firth, J. K. Taubenberger and P. Digard (2012).
Science 337(6091): 199-204.
DOI: 10.1126/science.1222213. (1,442kB)
uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs.
Ivanov, I. P., G. Loughran and J. F. Atkins (2008).
Proc Natl Acad Sci U S A 105(29): 10079-10084.
DOI: 10.1073/pnas.0801590105. (765kB)
Translational bypassing without peptidyl-tRNA anticodon scanning of coding gap mRNA.
Wills, N. M., M. O'Connor, C. C. Nelson, C. C. Rettberg, W. M. Huang, R. F. Gesteland and J. F. Atkins (2008).
EMBO J 27(19): 2533-2544.
DOI: 10.1038/emboj.2008.170. (314kB)