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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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University of Utah
Schools of Medicine
Salt Lake City
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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
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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
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