MAMMALIAN ORTHOLOGUES OF A YEAST REGULATOR OF NONSENSE TRANSCRIPT STABILITY

All eukaryotes that have been studied to date possess the ability to d etect and degrade transcripts that contain a premature signal for the termination of translation, This process of nonsense-mediated RNA deca y has been most comprehensively studied in the yeast Saccharomyces cer evisiae where at least three trans-acting factors (Upf1p through Upf3p ) are required, We have cloned cDNAs encoding human and murine homolog ues of Upf1p, termed rent1 (regulator of nonsense transcripts), Rent1 is the first identified mammalian protein that contains all of the put ative functional elements in Upf1p including zinc finger-like and NTPa se domains, as well as all motifs common to members of helicase superf amily I, Moreover, expression of a chimeric protein, containing the ce ntral region of rent1 flanked by the extreme N and C termini of Upf1p, complements the Upf1p-deficient phenotype in yeast, Thus, despite app arent differences between yeast and mammalian nonsense-mediated RNA de cay, these data suggest that the two pathways use functionally related machinery.