Department of Biomolecular Chemistry, Nijmegen Center for Molecular Life Sciences, Institute for Molecules and Materials, Radboud University Nijmegen, The Netherlands.
Wiley Interdiscip Rev RNA. 2010 Jul-Aug;1(1):102-16. doi: 10.1002/wrna.9. Epub 2010 May 6.
The human RNase MRP complex consists of a catalytic RNA and several protein components. RNase MRP is a ubiquitously expressed eukaryotic endoribonuclease that cleaves various RNAs, including ribosomal, messenger, and mitochondrial RNAs, in a highly specific fashion. In several autoimmune diseases autoantibodies targeting RNase MRP have been found. These so-called anti-Th/To autoantibodies, which most frequently can be detected in the sera of scleroderma patients, are directed to several protein components of the RNase MRP and the evolutionarily related RNase P complex. It is not yet known whether the anti-Th/To immune response is an epiphenomenon or whether these autoantibodies play a role in the pathophysiology of the disease. The gene encoding the RNase MRP RNA was the first nuclear non-coding RNA gene demonstrated to be associated with a genetic disease. Mutations in this gene are causing the highly pleiotropic disease cartilage-hair hypoplasia (CHH). CHH patients are characterized by a short stature, hypoplastic hair, and short limbs. In addition, they show a predisposition to lymphomas and other cancers and suffer from defective T-cell immunity. Since the identification of the first CHH-associated mutations in 2001, many distinct mutations have been found in different patients. These mutations either affect the structure of the RNase MRP RNA or are located in the promoter region and reduce the expression levels. In this review article we will, after describing the biochemical aspects of RNase MRP, discuss the targeting of RNase MRP in autoimmunity and the role of mutations in the RNase MRP RNA gene in CHH.
人 RNase MRP 复合物由一个催化 RNA 和几个蛋白质组成。RNase MRP 是一种广泛表达的真核内切核酸酶，以高度特异性方式切割各种 RNA，包括核糖体 RNA、信使 RNA 和线粒体 RNA。在几种自身免疫性疾病中，已发现针对 RNase MRP 的自身抗体。这些所谓的抗-Th/To 自身抗体，最常可在硬皮病患者的血清中检测到，针对 RNase MRP 的几个蛋白质组成部分和进化上相关的 RNase P 复合物。目前尚不清楚抗-Th/To 免疫反应是一种偶然现象，还是这些自身抗体在疾病的病理生理学中发挥作用。编码 RNase MRP RNA 的基因是第一个被证明与遗传疾病相关的核非编码 RNA 基因。该基因的突变导致高度多态性疾病软骨毛发发育不良 (CHH)。CHH 患者的特征是身材矮小、毛发发育不良和四肢短小。此外，他们易患淋巴瘤和其他癌症，并患有 T 细胞免疫缺陷。自 2001 年首次发现与 CHH 相关的突变以来，已在不同患者中发现了许多不同的突变。这些突变要么影响 RNase MRP RNA 的结构，要么位于启动子区域并降低表达水平。在这篇综述文章中，我们将在描述 RNase MRP 的生化方面后，讨论 RNase MRP 在自身免疫中的靶向作用以及 RNase MRP RNA 基因突变在 CHH 中的作用。
