The SnoRNA MBII-52 (SNORD 115) is Processed into Smaller RNAs and Regulates Alternative Splicing

Overview

Journal Hum Mol Genet

Specialties Genetics
Molecular Biology

Date 2010 Jan 8

PMID 20053671

Citations 153

Authors

Shivendra Kishore

Amit Khanna

Zhaiyi Zhang

Jingyi Hui

Piotr J Balwierz

Mihaela Stefan

Carol Beach

Robert D Nicholls

Mihaela Zavolan

Stefan Stamm

Affiliations

Soon will be listed here.

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.

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