Division of Molecular Genetics and Cancer, Nitte University Centre for Science Education & Research, NITTE (Deemed to be University), Deralakatte, Mangaluru, 575018, India.
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Sci Rep. 2023 Jun 20;13(1):10026. doi: 10.1038/s41598-023-37226-6.
Poly (A)-specific ribonuclease (PARN) is the most important 3'-5'exonuclease involved in the process of deadenylation, the removal of poly (A) tails of mRNAs. Although PARN is primarily known for its role in mRNA stability, recent studies suggest several other functions of PARN including a role in telomere biology, non-coding RNA maturation, trimming of miRNAs, ribosome biogenesis and TP53 function. Moreover, PARN expression is de-regulated in many cancers, including solid tumours and hematopoietic malignancies. To better understand the in vivo role of PARN, we used a zebrafish model to study the physiological consequences of Parn loss-of-function. Exon 19 of the gene, which partially codes for the RNA binding domain of the protein, was targeted for CRISPR-Cas9-directed genome editing. Contrary to the expectations, no developmental defects were observed in the zebrafish with a parn nonsense mutation. Intriguingly, the parn null mutants were viable and fertile, but turned out to only develop into males. Histological analysis of the gonads in the mutants and their wild type siblings revealed a defective maturation of gonadal cells in the parn null mutants. The results of this study highlight yet another emerging function of Parn, i.e., its role in oogenesis.
聚（A）特异性核糖核酸酶（PARN）是参与脱腺苷酸化过程的最重要的 3'-5'外切核酸酶，该过程会移除 mRNA 的聚（A）尾巴。尽管 PARN 主要因其在 mRNA 稳定性中的作用而被人们所知，但最近的研究表明 PARN 具有其他几种功能，包括在端粒生物学、非编码 RNA 成熟、miRNA 修剪、核糖体生物发生和 TP53 功能中的作用。此外，PARN 的表达在许多癌症中失调，包括实体瘤和血液恶性肿瘤。为了更好地了解 PARN 的体内作用，我们使用斑马鱼模型来研究 Parn 功能丧失的生理后果。该基因的exon 19 部分编码该蛋白的 RNA 结合结构域，是针对 CRISPR-Cas9 指导的基因组编辑的目标。与预期相反，带有 parn 无义突变的斑马鱼没有观察到发育缺陷。有趣的是，parn 缺失突变体是有活力和可育的，但结果只发育成雄性。对突变体和其野生型同窝仔鱼的性腺的组织学分析显示，parn 缺失突变体中的性腺细胞成熟有缺陷。这项研究的结果强调了 PARN 的另一个新兴功能，即其在卵母细胞发生中的作用。
