The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing

Shivendra Kishore, Amit Khanna, Zhaiyi Zhang, Jingyi Hui, Piotr J. Balwierz, Mihaela Stefan, Carol Beach, Robert D. Nicholls, Mihaela Zavolan, Stefan Stamm

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

The loss of HBII-52 and related C/D box small nucleolar RNA (snoRNA) expression units have been implicated as a cause for the Prader-Willi syndrome (PWS). We recently found that the C/D box snoRNA HBII-52 changes the alternative splicing of the serotonin receptor 2C pre-mRNA, which is different from the traditional C/D box snoRNA function in non-mRNA methylation. Using bioinformatic predictions and experimental verification, we identified five pre-mRNAs (DPM2, TAF1, RALGPS1, PBRM1 and CRHR1) containing alternative exons that are regulated by MBII-52, the mouse homolog of HBII-52. Analysis of a single member of the MBII-52 cluster of snoRNAs by RNase protection and northern blot analysis shows that the MBII-52 expressing unit generates shorter RNAs that originate from the full-length MBII-52 snoRNA through additional processing steps. These novel RNAs associate with hnRNPs and not with proteins associated with canonical C/D box snoRNAs. Our data indicate that not a traditional C/D box snoRNA MBII-52, but a processed version lacking the snoRNA stem is the predominant MBII-52 RNA missing in PWS. This processed snoRNA functions in alternative splice-site selection. Its substitution could be a therapeutic principle for PWS.

Original languageEnglish (US)
Article numberddp585
Pages (from-to)1153-1164
Number of pages12
JournalHuman molecular genetics
Volume19
Issue number7
DOIs
StatePublished - Jan 6 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Kishore, S., Khanna, A., Zhang, Z., Hui, J., Balwierz, P. J., Stefan, M., Beach, C., Nicholls, R. D., Zavolan, M., & Stamm, S. (2010). The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing. Human molecular genetics, 19(7), 1153-1164. [ddp585]. https://doi.org/10.1093/hmg/ddp585