(A) Pre-rRNA (blue) hybridizes with H/ACA snoRNAs to isomerize uridine (U) to pseudouridine (Ψ, red) and with C/D snoRNAs to methylate ribose at the 2′-position (CH3, red). (B) Pre-rRNA is modified while transcribed by RNA polymerase I (Pol I). (C) Only segments incorporated into mature ribosomes are modified (sites are represented by Ψs, red). But how does each snoRNA find its target? (D) Some snoRNA-guided modifications occur in double-stranded regions of mature rRNA (1) and next to each other (2 and 3) presenting potential clashes of two hybrids (circled red). (E) Transcribing Pol I forms trains on rDNA genes, from which nascent pre-rRNAs emerge in a Christmas tree–like fashion on electron microscope grids. This occurs in the dense fibrillar component (DFC) of the nucleolus enveloped in a cloud of snoRNPs looking for target nucleotides to modify and rendering the DFC akin to a beehive.
