PROCESSING OF FIBRILLARIN-ASSOCIATED SNORNAS FROM PRE-MESSENGER-RNA INTRONS - AN EXONUCLEOLYTIC PROCESS EXCLUSIVELY DIRECTED BY THE COMMON STEM-BOX TERMINAL STRUCTURE

Nucleoli contain complex populations of small nucleolar RNAs (snoRNAs) likely to be involved in pre-rRNA processing and ribosome biogenesis. A growing family of snoRNAs which interacts with nucleolar protein fi brillarin is structurally related by the presence of long complementar ities to rRNA (12 to 21 nucleotides) and of a pair of common sequence motifs, termed boxes C and D. All are encoded in introns and produced by processing of intronic RNA. We have analysed the mechanism of proce ssing of one of these snoRNAs, U20, by transfection in mouse cells. We show here that the cia-acting signals for its processing are restrict ed to a minor portion of the mature snoRNA sequence. A terminal struct ure in which the two box moths are brought in close vicinity by the pa iring of the 5' and 3' terminal nucleotides is sufficient to direct fa ithful processing. Particularly, the key role of the terminal stem sha red by most snoRNAs of this family is demonstrated by the effect of co mpensatory mutations. Our results also indicate that faithful processi ng at both ends of the snoRNA can be uncoupled and that it is not stri ctly dependent on pre-mRNA splicing. Finally, our data point to the ex clusive involvement of 5'-->3' and 3'-->5' exonucleolytic activities i n the processing of intronic snoRNAs of this family.