The RNA component of human telomerase (hTR) includes H/ACA and CR7 domains required for 3' end processing, localization, and accumulation. The terminal loop of the CR7 domain contains the CAB box (ugAG) required for targeting of scaRNAs to Cajal bodies (CB) and an uncharacterized sequence required for accumulation and processing. To dissect out the contributions of the CR7 stem loop to hTR processing and localization, we solved the solution structures of the 3' terminal stem loops of hTR CR7 and U64 H/ACA snoRNA, and the 5' terminal stem loop of U85 C/D-H/ACA scaRNA. These structures, together with analysis of localization, processing, and accumulation of hTRs containing nucleotide substitutions in the CR7 domain, identified the sequence and structural requirements of the hTR processing and CB localization signals and showed that these signals are functionally independent. Further, 3' end processing was found to be a prerequisite for translocation of hTR to CBs.

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Fragile X syndrome, the most common inherited form of mental retardation, arises in individuals with more than 200 CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 ( FMR1) gene. Although CGG repeat numbers comparable to those found in the normal human population are found in various non-human primates, neither the within-species size variation nor the propensity for expansion of the CGG repeat has been described for any non-human primate species. The allele distribution has now been determined for FMR1 (homologue) CGG repeats of 265 unrelated founder females of Macaca mulatta monkeys. Among 530 X chromosomes, at least 26 distinct repeat lengths were identified, ranging from 16 to 54 CGG repeats. Of these alleles 79% have between 25 and 33 CGG repeats. Detailed examination of the CGG region revealed a conserved G (CGG)(2 )G interruption, although in no case was an AGG trinucleotide detected. Two animals carried borderline premutation alleles with 54 CGG repeats, within the region of marginal instability for humans. Thus, M. mulatta may be useful as an animal model for the study of fragile X syndrome.

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