Regulatory Role of Small Nucleolar RNAs in Human Diseases

Stepanov, Grigory A.; Filippova, Julia A.; Komissarov, Andrey B.; Kuligina, Elena V.; Richter, Vladimir A.; Semenov, Dmitry V.

The relation between box C/D RNAs and neurodegenerative disease development has been also described [67, 68] . In a series of independent studies the genetic disorder, Prader-Willi syndrome (PWS), was shown to be caused by the loss of paternal gene expression from a maternally imprinted region 15q11-q13 on chromosome 15. The disease is featured by mental retardation, low height, obesity, and muscle hypotonia. Locus 15q11-q13 contains numerous copies of two box C/D RNAs-SNORD115 (HBII-52) and SNORD116 (HBII-85) [16] . Box C/D RNA SNORD115 may have an impact on 5-HT2CR serotonin receptor mRNA level in brain [19, 20] . The loss of the SNORD116 snoRNAs can be a significant contribution to the etiology of PWS [16, 69, 70] . The deletion of PWS critical region that contains the SNURF-SNRPN locus, as it has been demonstrated in mouse model of PWS, leads to the changes in splicing patterns of several pre-mRNAs [18] . The data also indicates that SNORD115, as well as SNORD116, undergoes specific hydrolysis forming smaller fragments, processed snoRNAs referred to as "psnoR-NAs" [18, 22] . These processed species of SNORD115, but not the full-length snoRNA, were suggested to affect the outcome of alternative splicing of the pre-mRNAs [18] . However, Bortolin-Cavaillé and Cavaillé provided evidence against the existence of abundant processed variants of SNORD115 and SNORD116 (psnoRNAs) in human or mouse brain, concluding that PWS-encoded snoRNAs represent canonical box C/D snoRNAs [71] .