The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing
The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing
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snoRNA MBII-52 (SNORD 115) 被加工成更小的 RNA 并调节选择性剪接
DOI：
10.1093/hmg/ddp585
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发表时间：
2010-04-01
影响因子：
3.5
通讯作者：
Stamm, Stefan
中科院分区：
文献类型：
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作者：
Kishore, Shivendra;Khanna, Amit;Stamm, Stefan
HBII-52和相关的C/D盒小核仁RNA(SnoRNA)表达单位的缺失被认为是Prader-Willi综合征(PWS)的原因之一。我们最近发现，C/D盒snoRNA HBII-52改变了5-羟色胺受体2C前-mRNA的选择性剪接，这与传统的C/D盒snoRNA在非mRNA甲基化中的功能不同。利用生物信息学预测和实验验证，我们鉴定了五个含有可选外显子的前mRNAs(DPM2、TAF1、RALGPS1、PBRM1和CRHR1)，这些外显子受MBII-52(HBII-52的小鼠同源基因)调控。通过RNase保护和Northern印迹分析对MBII-52 snoRNA簇的单个成员进行分析表明，MBII-52表达单元通过额外的处理步骤产生来自全长MBII-52 snoRNA的较短RNA。这些新的RNAs与hnRNPs相关，而与典型的C/D盒snoRNAs相关的蛋白质不相关。我们的数据表明，不是传统的C/D盒snoRNA MBII-52，而是缺少snoRNA茎的加工版本是PWS中缺失的主要MBII-52 RNA。这种经过处理的snoRNA在选择性剪接位点选择中发挥作用。它的替代可能成为PWS的一种治疗原则。
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.