Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization
Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization
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DOI：
10.1073/pnas.250426397
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发表时间：
2000-12-19
影响因子：
11.1
通讯作者：
Hüttenhofer, A
中科院分区：
文献类型：
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作者：
Cavaillé, J;Buiting, K;Hüttenhofer, A
我们在小鼠和人体内鉴定了3个C/D-box小核仁rna （snoRNAs）和1个H/ACA-box小核仁rna （snoRNAs）。在小鼠中，所有四种snorna （MBII-13、MBII-52、MBII-85和mbii -36）都只在大脑中表达，这与所有其他已知的snorna不同。两种人类RNA同源物（HBII-52和hbii -36）共享这种表达模式，其余的HBII-13和HBII-85在该组织中普遍表达。在小鼠和人类中，脑特异性H/ACA盒snoRNA（分别为MBI-36和HBI-36）在脑特异性5 -羟色胺2C受体基因中被内含子编码。这三个人类C/D盒snorna定位于染色体15q11-q13，位于与Prader-Willi综合征（PWS）有关的区域，PWS是一种由父系基因表达不足引起的神经遗传性疾病。与其他C/D盒snorna不同，HBII-52和HBII-85这两个snorna分别以47或24个单元的串联重复阵列进行编码。在小鼠中，HBII-52的同源物是从串联重复序列的内含子部分加工而来的。有趣的是，这些snorna在PWS患者和PWS小鼠模型的皮层中缺失，表明它们的父系印记状态，并指出它们在PWS病因学中的潜在作用。尽管显示出两种普遍存在的snorna家族的特征，分别指导rRNA的2'- o -核糖甲基化和假尿嘧啶化，但它们缺乏任何明显的rRNA互补性。相反，脑特异性C/D盒snoRNA HBII-52与5 -羟色胺2C受体mRNA的关键片段具有18-nt的系统发育保守互补，这表明在该mRNA的加工中具有潜在作用。
We have identified three C/D-box small nucleolar RNAs (snoRNAs) and one H/ACA-box snoRNA in mouse and human. In mice, all four snoRNAs (MBII-13, MBII-52, MBII-85, and MBI-36) are exclusively expressed in the brain, unlike all other known snoRNAs. Two of the human RNA orthologues (HBII-52 and HBI-36) share this expression pattern, and the remainder, HBII-13 and HBII-85, are prevalently expressed in that tissue. In mice and humans, the brain-specific H/ACA box snoRNA (MBI-36 and HBI-36, respectively) is intron-encoded in the brain-specific serotonin 2C receptor gene. The three human C/D box snoRNAs map to chromosome 15q11-q13, within a region implicated in the Prader-Willi syndrome (PWS), which is a neurogenetic disease resulting from a deficiency of paternal gene expression. Unlike other C/D box snoRNAs, two snoRNAs, HBII-52 and HBII-85, are encoded in a tandemly repeated array of 47 or 24 units, respectively. In mouse the homologue of HBII-52 is processed from intronic portions of the tandem repeats. Interestingly, these snoRNAs were absent from the cortex of a patient with PWS and from a PWS mouse model, demonstrating their paternal imprinting status and pointing to their potential role in the etiology of PWS. Despite displaying hallmarks of the two families of ubiquitous snoRNAs that guide 2'-O-ribose methylation and pseudouridylation of rRNA, respectively, they lack any telltale rRNA complementarity. Instead, brain-specific C/D box snoRNA HBII-52 has an 18-nt phylogenetically conserved complementarity to a critical segment of serotonin 2C receptor mRNA, pointing to a potential role in the processing of this mRNA.