Fig. 2. Biogenesis and function of 2′-O-methylation and pseudouridylation guide snoRNAs. In mammalian cells, all guide RNAs are synthesized within introns of pre-mRNAs in the nucleoplasm. Most intronic snoRNAs are processed from the removed and debranched host intron by exonucleolytic activities. It remains unclear whether 5′ and 3′ end processing of snoRNAs occurs already in the nucleoplasm, or later in the nucleolus. Guide snoRNAs accumulating in the nucleolus direct 2′-O-methylation and pseudouridylation of the 18S, 5.8S and 28S rRNAs, the U6 snRNA and perhaps other cellular RNAs, including tRNAs, the signal recognition particle (SRP) and telomerase RNAs. It seems that box C/D, but not box H/ACA snoRNAs, transiently appear in the Cajal body before accumulating in the nucleolus. Some guide RNAs (scaRNAs) directing modification of the pol II-transcribed spliceosomal snRNAs accumulate in the Cajal body (CB). For other details, see the text.