Small nucleolar RNAs (snoRNAs) guide the site-specific modification of nucleotides in target RNAs by two types of modifications first being 2'-O-ribose methylation and secondly pseudouridylation, directed by two large families of snoRNAs termed box C/D and box H/ACA snoRNAs, respectively. SnoRNAs recognize target sequences by formation of a canonical guide RNA duplex and recruit associated proteins to perform the corresponding modification at the target site. Generally, snoRNAs range between 60 and 300 nucleotides in length, but only short sequences participate in target recognition via antisense interactions. Chromosome 15 harbors SNURF-SNRPN locus that encodes several evolutionarily conserved C/D box small nucleolar RNAs (snoRNAs) namely: HBII-13, -436, -437, -438, -85 and -52 and is linked with the Prader-Willi syndrome (PWS), that happens to be a congenital genetic disorder which is caused by the loss of paternal gene expression from a maternally imprinted region on chromosome 15 encoding SNURF-SNRPN locus.

No evidence of mutations with phenotypic consequences have been recorded in snoRNA sequences, which suggest that they are lethal, functionally redundant or may cause subtle effects such as on growth or brain function. It has been reported that certain snoRNAs, present as multicopy genes (designated as HBII-52 and HBII-85 snoRNAs, respectively), are absent from the cortex of a patient with Prader–Willi Syndrome (PWS) and from a PWS mouse model, demonstrating their paternal imprinting and pointing to their potential role in the etiology of PWS. However, a recent study of a genomic deletion of the HBII-52 snoRNA gene cluster in humans indicates that these snoRNAs do not play a major role in PWS on their own, or do so only in connection with the HBII-85 snoRNA cluster. In order to study the potential role of other snoRNAs in alternative splicing, I am cloning expression constructs for those snoRNAs particularly snoRNA -85 and -52 located in the SNURF-SNRPN region and making clones having multiple copies and in tandem, over express them in cell lines, and identify their targets by a genome-wide search using microarray technology. I am preparing nuclear extract from cells transfected with a snoRNA expression construct and use the HBII-52/serotonin receptor system as a model to test the influence of a snoRNP on alternative splicing in vitro.

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