SITE-SPECIFIC PSEUDOURIDINE FORMATION IN PRERIBOSOMAL RNA IS GUIDED BY SMALL NUCLEOLAR RNAS

During the nucleolar maturation of eukaryotic ribosomal RNAs, many sel ected uridines are converted into pseudouridine by a thus far undefine d mechanism. The nucleolus contains a large number of small RNAs (snoR NAs) that share two conserved sequence elements, box H and ACA. In thi s study, we demonstrate that site-specific pseudouridylation of rRNAs relies on short ribosomal signal sequences that are complementary to s equences in box H/ACA snoRNAs. Genetic depletion and reconstitution st udies on yeast snR5 and snR36 snoRNAs demonstrate that box H/ACA snoRN As function as guide RNAs in rRNA pseudouridylation. These results def ine a novel function for snoRNAs and further reinforce the idea that b ase pairing is the most common way to obtain specific substrate-''enzy me'' interactions during rRNA maturation.