The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing.
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.
Kishore
Shivendra
S
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
Khanna
Amit
A
Zhang
Zhaiyi
Z
Hui
Jingyi
J
Balwierz
Piotr J
PJ
Stefan
Mihaela
M
Beach
Carol
C
Nicholls
Robert D
RD
Zavolan
Mihaela
M
Stamm
Stefan
S
D017398:Alternative Splicing; D000818:Animals; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D051379:Mice; D011218:Prader-Willi Syndrome / Q000235:genetics*; D017393:RNA Editing; D012322:RNA Precursors; D020537:RNA, Small Nucleolar; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012322:RNA Precursors; D020537:RNA, Small Nucleolar; D044405:Receptor, Serotonin, 5-HT2C