The mRNA cap structure regulates transcription, translation, and mRNA stability. Although the enzyme activities required to generate a cap have been elucidated, the proteins containing each activity and their regulation have yet to be determined. The long-term research objective is to determine the mechanisms for modulating cap formation and how these mechanisms are altered for tumor formation. This work will be initiated by studying the guanylytransferase lambda 2 of reovirus. The two specific aims of this research proposal are: (1) to localize the catalytic domain by proteolytic deletional and point mutagenesis analysis; (2) to determine the modulators using genetic screens for activity in yeast.