Dyskerin and its homologs are ancient and conserved enzymes that catalyze the most common post-transcriptional modification found in cells, pseudouridylation. The resulting pseudouridines provide stability to RNA molecules and regulate ribosome biogenesis and splicing events. Dyskerin does not act independently—it is the core component of a protein heterotetramer, which associates with RNAs that contain the H/ACA motif. The variety of H/ACA RNAs that guide the function of this ribonucleoprotein (RNP) complex highlights the diversity of cellular processes in which dyskerin participates. When associated with small nucleolar (sno) RNAs, it regulates ribosomal (r) RNAs and ribosome biogenesis. By interacting with small Cajal body (sca) RNAs, it targets small nuclear (sn) RNAs to regulate pre-mRNA splicing. As a component of the telomerase holoenzyme, dyskerin binds to the telomerase RNA to modulate telomere maintenance. In a disease context, dyskerin malfunction can result in multiple detrimental phenotypes. Mutations in DKC1, the gene that encodes dyskerin, cause the premature aging syndrome X-linked dyskeratosis congenita (X-DC), a still incurable disorder that typically leads to bone marrow failure. In this review, we present the classical and most recent findings on this essential protein, discussing the evolutionary, structural, and functional aspects of dyskerin and the H/ACA RNP. The latest research underscores the role that dyskerin plays in the regulation of gene expression, translation efficiency, and telomere maintenance, along with the impacts that defective dyskerin has on aging, cell proliferation, haematopoietic potential, and cancer.

中文翻译：

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Dyskerin：一种必需的假尿苷合酶，在核糖体生物发生、剪接和端粒维持中具有多方面的作用

Dyskerin 及其同系物是古老且保守的酶，可催化细胞中最常见的转录后修饰，假尿苷化。由此产生的假尿苷为 RNA 分子提供稳定性并调节核糖体生物发生和剪接事件。Dyskerin 不会独立发挥作用——它是蛋白质异四聚体的核心成分，与含有 H/ACA 基序的 RNA 结合。指导这种核糖核蛋白 (RNP) 复合物功能的 H/ACA RNA 的多样性突出了肌张力蛋白参与的细胞过程的多样性。当与小核仁 (sno) RNA 相关时，它调节核糖体 (r) RNA 和核糖体生物合成。通过与小 Cajal 体 (sca) RNA 相互作用，它靶向小核 (sn) RNA 来调节 pre-mRNA 剪接。作为端粒酶全酶的组成部分，dyskerin 与端粒酶 RNA 结合以调节端粒维持。在疾病背景下，皮肤肌动蛋白功能障碍可导致多种有害表型。中的突变DKC1是一种编码角化不良的基因，会导致早衰综合征 X 连锁先天性角化不良 (X-DC)，这是一种仍然无法治愈的疾病，通常会导致骨髓衰竭。在这篇综述中，我们介绍了关于这种必需蛋白质的经典和最新发现，讨论了肌张力蛋白和 H/ACA RNP 的进化、结构和功能方面。最新研究强调了肌动蛋白在调节基因表达、翻译效率和端粒维持方面的作用，以及有缺陷的肌动蛋白对衰老、细胞增殖、造血潜能和癌症的影响。