New clues to the function of the Cajal body.

New clues to the function of the Cajal body Small RNA molecules play major roles in a number of cellular functions. Depending on their predominant cellular location, small RNAs have been classified as nuclear (sn), nucleolar (sno) or cytoplasmic (sc). The nucleoplasmic species include the spliceosomal snRNAs (U1, U2, U4, U5 and U6) and the U7 snRNA required for histone pre-mRNA 3′-end formation. The snoRNAs are key players in the processing of ribosomal RNA (rRNA), and scRNAs function in protein synthesis. Most small RNAs have a complex life cycle, being synthesized as precursors that must undergo a series of processing events in order to become functionally mature. Many of these post-transcriptional modifications are 'guided' by other small RNAs and occur in specific cellular compartments such as the nucleolus (Filipowicz and Pogacic, 2002). Two related papers in The EMBO Journal from the groups of Tamás Kiss and Edouard Bertrand now highlight a role for Cajal bodies in the post-transcriptional modification of spliceosomal snRNAs and snoRNAs. Kiss and co-workers report a new family of small RNAs that localize specifically to Cajal bodies and are involved in the maturation of spliceosomal snRNAs (Darzacq et al., 2002), and Bertrand and co-workers show that the final processing steps involved in the biogenesis of U3 snoRNA take place in Cajal bodies (Verheggen et al., 2002). Despite being identified around 100 years ago by the neuro-cytologist Ramon y Cajal, the function of Cajal bodies has so far proved elusive. When viewed with the electron microscope, these subnuclear 'organelles' appear to consist of a tangle of coiled threads and were hence also referred to as coiled bodies. Since they contain U7 snRNA and components of the three RNA polymerase transcription complexes, they have been proposed to be involved in the assembly of the transcriptional machinery and U7-dependent histone mRNA 3′-end processing (Gall, 2000). Furthermore, Cajal bodies are highly enriched in spliceo-somal snRNAs, which contain many 2′-O-ribose-methylated nucleotides and pseudouridines (Reddy and Busch, 1988). Kiss and co-workers have now discovered a novel family of Cajal-body-specific small RNAs (termed scaRNAs) that have the potential to base-pair with the U snRNAs and are likely to function as guides for the site-specific 2′-O-ribose methylation and pseudouridine formation in U1, U2, U4 and U5 snRNAs (Darzacq et al., 2002; Figure 1A). Two of these authors have recently described an unusual small RNA, the U85 RNA (Jády and Kiss, 2001); now, in their latest …