Department of Biomolecular Chemistry, Nijmegen Centre for Molecular Life Sciences, Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.
Cell Mol Life Sci. 2011 Jul;68(14):2469-80. doi: 10.1007/s00018-010-0568-3. Epub 2010 Oct 30.
RNase MRP is a conserved endoribonuclease, in humans consisting of a 267-nucleotide RNA associated with 7-10 proteins. Mutations in its RNA component lead to several autosomal recessive skeletal dysplasias, including cartilage-hair hypoplasia (CHH). Because the known substrates of mammalian RNase MRP, pre-ribosomal RNA, and RNA involved in mitochondrial DNA replication are not likely involved in CHH, we analyzed the effects of RNase MRP (and the structurally related RNase P) depletion on mRNAs using DNA microarrays. We confirmed the upregulation of the interferon-inducible viperin mRNA by RNAi experiments and this appeared to be independent of the interferon response. We detected two cleavage sites for RNase MRP/RNase P in the coding sequence of viperin mRNA. This is the first study providing direct evidence for the cleavage of a mRNA by RNase MRP/RNase P in human cells. Implications for the involvement in the pathophysiology of CHH are discussed.
核糖核酸酶 MRP 是一种保守的内切核酸酶，在人类中由与 7-10 种蛋白质相关的 267 个核苷酸 RNA 组成。其 RNA 成分的突变导致几种常染色体隐性骨骼发育不良，包括软骨毛发发育不良（CHH）。由于已知哺乳动物核糖核酸酶 MRP 的底物、核糖体前 RNA 和参与线粒体 DNA 复制的 RNA 不太可能参与 CHH，我们使用 DNA 微阵列分析了核糖核酸酶 MRP（和结构上相关的核糖核酸酶 P）耗竭对 mRNA 的影响。我们通过 RNAi 实验证实了 viperin mRNA 的干扰素诱导上调，这似乎与干扰素反应无关。我们在 viperin mRNA 的编码序列中检测到两个核糖核酸酶 MRP/核糖核酸酶 P 的切割位点。这是第一项在人类细胞中提供核糖核酸酶 MRP/核糖核酸酶 P 切割 mRNA 的直接证据的研究。讨论了其在 CHH 病理生理学中的参与的意义。
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