Transfer RNAs are essential components of all biological systems. Although the role of tRNA in protein synthesis is usually emphasized it is important to recognize that the molecule is involved in a variety of other biological functions: reverse transcription of RNA to DNA in the retroviruses; regulation of enzyme synthesis; regulation of cell division; and changes in tRNA populations during embryogenesis and oncogenesis. It is not clear why the tRNA molecule is used in such a large variety of biological functions or how the sequence diversities necessary to achieve these functions are generated. This proposal implements genetics, biochemistry, and statistics as converging operations to analyze tRNA, therein allowing the disclosure of unprecedented information about the molecule. We propose to elucidate: - the nucleotide domains of the 20 tRNA classes responsible for their amino acid specificities; - the merits of our scheme for the origin and evolution of primitive tRNA molecules (continuing 9-19 nucleotides) that encoded 4 classes of amino acids distinguished only grossly by the general chemical nature of their functional side chains. By extention, the statistical and mathematical methods we develop can readily be adapted to a number of important questions related to health problems. For example, they are readily adaptable to influenza viruses to determine how the 8 genomic RNAs necessary for flus' viral activity are recognized as distinct during virion assembly. Such knowledge could then be used to prevent assembly (and thus disease) in a manner that does not adversely impact on the physiology of the host cell(s). Also amenable to study (with potential for cure) is the assembly of the oncogenic retrovirus, for their virions contain one specific tRNA and two """"""""35S genomic"""""""" RNAs.
