Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.
Clin Chim Acta. 2010 Dec 14;411(23-24):1862-8. doi: 10.1016/j.cca.2010.08.033. Epub 2010 Aug 31.
ZC3H12A is a gene whose absence is related to autoimmune disorders and to other phenotypical alterations.
A comprehensive review of the structure, molecular functions and regulation of ZC3H12A gene and its protein MCPIP1 is done in order to understand their clinical implications.
ZC3H12A, at 1p34.3, has 9860bp, six exons and 61 described SNPs. Eleven are non-synonymous thus leading to changes in MCPIP1, the protein encoded by ZC3H12A. MCPIP1 is induced by MCP-1 and IL-1 whose signals are transduced through the NF-kβ and MAPkinase pathways. This protein acts as an RNAse by degrading chemokine transcripts such as IL-1 as well as its own mRNA and as a transcription factor by reducing the expression of other chemokines induced by NF-kβ such as MCP-1. It also up-regulates genes involved in several differentiation processes and apoptosis. Therefore, ZC3H12A is an equilibrium gatekeeper that not only regulates its own inducers but also controls the regulation by degrading its own mRNA.
Understanding ZC3H12A gives a comprehensive panorama that promises to improve our understanding of processes in which this gene is involved including autoimmune, infectious and cardiovascular diseases.
ZC3H12A 是一种与自身免疫性疾病和其他表型改变有关的基因。
为了了解其临床意义，对 ZC3H12A 基因及其编码蛋白 MCPIP1 的结构、分子功能和调控进行了全面综述。
位于 1p34.3 的 ZC3H12A 基因有 9860bp，6 个外显子和 61 个已描述的 SNP。其中 11 个是非同义 SNP，导致 MCPIP1 发生变化，MCPIP1 是由 ZC3H12A 编码的蛋白。MCPIP1 由 MCP-1 和 IL-1 诱导，其信号通过 NF-kβ 和 MAPkinase 途径转导。这种蛋白作为 RNA 酶，通过降解趋化因子转录本（如 IL-1）及其自身的 mRNA，以及作为转录因子，通过降低 NF-kβ 诱导的其他趋化因子（如 MCP-1）的表达，来发挥作用。它还上调参与几种分化过程和细胞凋亡的基因。因此，ZC3H12A 是一个平衡的守门员，不仅调节自身的诱导物，而且通过降解自身的 mRNA 来控制调节。
了解 ZC3H12A 提供了一个全面的全景，有望提高我们对该基因参与的包括自身免疫、感染和心血管疾病在内的多个过程的理解。
