Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization

We have identified three C/D-box small nucleolar RNAs (snoRNAs) and one H/A CA-box snoRNA in mouse and human. In mice, all four snoRNAs (MBII-13, MBII- 52, MBII-85, and MBI-36) are exclusively expressed in the brain, unlike all other known snoRNAs. Two of the human RNA orthologues (HBII-52 and HBI-36) share this expression pattern, and the remainder, HBII-13 and HBII-85, are prevalently expressed in that tissue. In mice and humans, the brain-specif ic H/ACA box snoRNA (MBI-36 and HBI-36, respectively) is intron-encoded in the brain-specific serotonin 2C receptor gene. The three human C/D box snoR NAs map to chromosome 15q11-q13, within a region implicated in the Prader-W illi syndrome (PWS), which is a neurogenetic disease resulting from a defic iency of paternal gene expression. Unlike other C/D box snoRNAs, two snoRNA s, HBII-52 and HBII-85, are encoded in a tandemly repeated array of 47 or 2 4 units, respectively. In mouse the homologue of HBII-52 is processed from intronic portions of the tandem repeats. Interestingly, these snoRNAs were absent from the cortex of a patient with PWS and from a PWS mouse model, de monstrating their paternal imprinting status and pointing to their potentia l role in the etiology of PWS. Despite displaying hallmarks of the two fami lies of ubiquitous snoRNAs that guide 2'-O-ribose methylation and pseudouri dylation of rRNA, respectively, they lack any telltale rRNA complementarity . Instead, brain-specific C/D box snoRNA HBII-52 has an 18-nt phylogenetica lly conserved complementarity to a critical segment of serotonin 2C recepto r mRNA, pointing to a potential role in the processing of this mRNA.