THE SNORNA BOX C D MOTIF DIRECTS NUCLEOLAR TARGETING AND ALSO COUPLESSNORNA SYNTHESIS AND LOCALIZATION/

Most small nucleolar RNAs (snoRNAs) fall into two families, known as t he box C/D and box H/ACA snoRNAs, The various box elements are essenti al for snoRNA production and for snoRNA-directed modification of rRNA nucleotides, In the case of the box C/D snoRNAs, boxes C and D and an adjoining stem form a vital structure, known as the box C/D motif, Her e, we examined expression of natural and artificial box C/D snoRNAs in yeast and mammalian cells, to assess the role of the box C/D motif in snoRNA localization. The results demonstrate that the motif is necess ary and sufficient for nucleolar targeting, both in yeast and mammals. Moreover, in mammalian cells, RNA is targeted to coiled bodies as wel l. Thus, the box C/D motif is the first intranuclear RNA trafficking s ignal identified for an RNA family. Remarkably, it also couples snoRNA localization with synthesis and, most likely, function, The distribut ion of snoRNA precursors in mammalian cells suggests that this couplin g is provided by a specific protein(s) which binds the box C/D motif d uring or rapidly after snoRNA transcription. The conserved nature of t he box C/D moth indicates that its role in coupling production and loc alization of snoRNAs is of ancient evolutionary origin.