The readout of the genetic code is subject to redirection at specific places in a minority of mRNAs in probably all organisms. This recoding, or reprogramming of the genetic code, is under dynamic control of mRNA information through the combination of specific codons and other signals. (It is in contrast to the 'hard-wired') exceptions to the 'universal' code in niches such as some mitochondria where specific codons in all mRNAs have a new meaning.) An investigation of two cases is proposed: (1) Bypassing, where ribosomes translate over a coding gap in mRNA. In decoding phage T4 gene 60, fifty nucleotides present in the mature mRNA between codons 46 and 47 are bypassed with high efficiency. An investigation of the mRNA signals, a critical region of the nascent peptide and ribosome components that interact with these enabling elements is proposed. (2) Programmed frameshifting. In the first mammalian cellular example, an obligatory +1 ribosomal frameshift is required early in decoding the genes for rat and human antizyme. This frameshifting is governed by the level of polyamines and constitutes the key point in an autoregulatory circuit. An investigation of mRNA signals is proposed. A novel 5 prime element will be defined and regulation at alternate shift site codons characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM048152-08
Application #
6179579
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Rhoades, Marcus M
Project Start
1992-08-01
Project End
2001-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
8
Fiscal Year
2000
Total Cost
$317,255
Indirect Cost
Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Ivanov, Ivaylo P; Gesteland, Raymond F; Atkins, John F (2006) Evolutionary specialization of recoding: frameshifting in the expression of S. cerevisiae antizyme mRNA is via an atypical antizyme shift site but is still +1. RNA 12:332-7
Baranov, Pavel V; Fayet, Olivier; Hendrix, Roger W et al. (2006) Recoding in bacteriophages and bacterial IS elements. Trends Genet 22:174-81
Christensen, Greg L; Ivanov, Ivaylo P; Atkins, John F et al. (2006) Identification of polymorphisms in the Hrb, GOPC, and Csnk2a2 genes in two men with globozoospermia. J Androl 27:11-5
Zook, Matthew B; Howard, Michael T; Sinnathamby, Gomathinayagam et al. (2006) Epitopes derived by incidental translational frameshifting give rise to a protective CTL response. J Immunol 176:6928-34
Wills, Norma M; Moore, Barry; Hammer, Andrew et al. (2006) A functional -1 ribosomal frameshift signal in the human paraneoplastic Ma3 gene. J Biol Chem 281:7082-8
Gurvich, Olga L; Baranov, Pavel V; Gesteland, Raymond F et al. (2005) Expression levels influence ribosomal frameshifting at the tandem rare arginine codons AGG_AGG and AGA_AGA in Escherichia coli. J Bacteriol 187:4023-32
Howard, Michael T; Aggarwal, Gaurav; Anderson, Christine B et al. (2005) Recoding elements located adjacent to a subset of eukaryal selenocysteine-specifying UGA codons. EMBO J 24:1596-607
Bucklin, Douglas J; Wills, Norma M; Gesteland, Raymond F et al. (2005) P-site pairing subtleties revealed by the effects of different tRNAs on programmed translational bypassing where anticodon re-pairing to mRNA is separated from dissociation. J Mol Biol 345:39-49
Baranov, Pavel V; Henderson, Clark M; Anderson, Christine B et al. (2005) Programmed ribosomal frameshifting in decoding the SARS-CoV genome. Virology 332:498-510
Zhang, Yan; Baranov, Pavel V; Atkins, John F et al. (2005) Pyrrolysine and selenocysteine use dissimilar decoding strategies. J Biol Chem 280:20740-51

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