John F. Atkins
Research Professor of Human Genetics
B.A. Dublin University
Ph.D. Dublin University
Sc.D. Dublin University
John Atkin's PubMed Literature Search
Research
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 function of recoding.
Our recent work has focused substantially on novel viral occurrences of recoding – it is especially prevalent in viral and chromosomal mobile element decoding. However, we are now concentrating more on utilization of recoding in chromosomal gene decoding. Particular mRNA structures 3' of the recoding site are well known as stimulators of recoding, though in one case we are currently investigating, intra-mRNA structure does not seem to be involved – in this we are investigating the possibility of mRNA in the ribosome entrance tunnel pairing with ribosomal RNA. Nevertheless, most of our current effort on stimulators is the interaction of nascent peptide sequence while still within the ribosome, interacting with ribosomal components of the peptide exit tunnel to mediate recoding. Also in a case of translational bypassing we have evidence for mRNA structure formation within the ribosome. In collaboration with Drs. M.T. Howard and K. Flanigan we are also studying drug induced readthrough of premature stop codons as a prelude to tests for the amelioration of symptoms of a subset of human genetic disease.
One fascinating case of codon redefinition is how the 10 UGA codons within human selenoprotein P specifies the 21st amino acid selenocysteine rather than termination. In collaboration with Mike Howard, Sen Wu, Mario Capecchi and others we are investigating mice which have mutants in the recoding signals involved
References
1. Atkins JF, Gesteland RF, Cech TR (eds) (2011) RNA Worlds: From life’s origins to diversity in gene regulation. 361 pages.Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. [Individual chapters also published in Cold Spring Harbor Perspectives in Biology]
2. Baranov PV, Wills NM, Barriscale KA, Firth AE, Jud MC, Letsou A, Manning G, Atkins JF (2011) Programmed ribosomal frameshifting in the expression of the regulator of intestinal stem cell proliferation, adenomatous polyposis coli (APC). RNA Biology, In press
3. Firth AE, Wills NM , Gesteland RF, Atkins JF (2011) Stimulation of stop codon readthrough: Frequent presence of an extended 3’ RNA structural element. Nucl Acids Res, e-pub ahead of print
4. Ivanov IP, Firth AE, Michel AM, Atkins JF and Baranov PV (2011) Identification of evolutionarily conserved non-AUG initiated N-terminal extensions in human coding sequences. Nucl Acids Res, e-pub ahead of print
5. Ivanov IP, Loughran G, Sachs MS, Atkins JF (2010) Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (eIF1). Proc Natl Acad Sci USA 107:18056-18060
6. Chung BYW, Firth AE, Atkins JF (2010) Frameshifting in alphaviruses: a diversity of 3′ stimulatory structures. J Mol Biol 397:448-456
7. Atkins JF, Baranov PV (2010) The distinction between recoding and reassignment. Genetics 185:1535-1536
8. Atkins JF, Gesteland RF (2010) eds. Recoding: Expansion of Decoding rules enriches gene expression. Springer, New York, 466 pages
9. Firth AE, Blitvich BJ, Wills NM, Miller CL, Atkins JF (2010) Evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses. Virol 399: 153-166
Updated 6/3/2011
