SNORD116 and SNORD115 change expression of multiple genes and modify each other's activity.

SNORD116 and SNORD115 change expression of multiple genes and modify each other's activity.
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DOI:
10.1016/j.gene.2015.07.023
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发表时间:
2015-11-10
期刊:
影响因子:
3.5
通讯作者:
Stamm S
Stamm S
中科院分区:
生物学3区
文献类型:
--
作者:
Falaleeva M;Surface J;Shen M;de la Grange P;Stamm S

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编码小核仁RNA的两个基因簇SNORD115和SNORD116的缺失导致了Prader-Willi综合征(PWS),这是人类最常见的肥胖症候群。SNORD115和SNORD116被认为是孤立的C/D盒snoRNAs(SNORD),因为它们不针对RNA或SnRNAs。SNORD115与5-羟色胺受体2C具有序列互补性,而SNORD116与已知RNA没有延伸的互补性。为了确定分子靶点,我们在HEK 293T细胞中单独或一起过表达SNORD115和SNORD116后,进行了全基因组阵列分析。我们发现SNORD116改变了200多个基因的表达。SNORD116主要改变mRNA的表达水平。令人惊讶的是,我们发现SNORD115改变了SNORD116对基因表达的影响。在类似的实验中,我们比较了PWS患者和年龄匹配的对照组患者死后下丘脑的基因表达。这些实验的概要导致了23个基因的表达水平受到SNORD116的影响。我们的结果表明,SNORD115和SNORD116影响多个基因的表达水平,并相互调节活性。
The loss of two gene clusters encoding small nucleolar RNAs, SNORD115 and SNORD116 contributes to Prader-Willi syndrome (PWS), the most common syndromic form of obesity in humans. SNORD115 and SNORD116 are considered to be orphan C/D box snoRNAs (SNORDs) as they do not target rRNAs or snRNAs. SNORD115 exhibits sequence complementarity towards the serotonin receptor 2C, but SNORD116 shows no extended complementarities to known RNAs. To identify molecular targets, we performed genome-wide array analysis after overexpressing SNORD115 and SNORD116 in HEK 293T cells, either alone or together. We found that SNORD116 changes the expression of over 200 genes. SNORD116 mainly changed mRNA expression levels. Surprisingly, we found that SNORD115 changes SNORD116’s influence on gene expression. In similar experiments, we compared gene expression in post-mortem hypothalamus between individuals with PWS and aged-matched controls. The synopsis of these experiments resulted in 23 genes whose expression levels were influenced by SNORD116. Together our results indicate that SNORD115 and SNORD116 influence expression levels of multiple genes and modify each other activity.
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