Division of Molecular Genetics and Cancer, Nitte University Centre for Science Education and Research (NUCSER), NITTE (Deemed to be University), Deralakate, Mangaluru 575018, India.
Consortium of Rare Genetic and Bone Marrow Disorders, India network@NitteDU, NITTE (Deemed to be University, Deralakatte, Mangaluru, India.
Life Sci. 2021 Nov 15;285:119953. doi: 10.1016/j.lfs.2021.119953. Epub 2021 Sep 11.
In eukaryotic cells, the balance between the synthesis and the degradation decides the steady-state levels of messenger RNAs (mRNA). The removal of adenosine residues from the poly(A) tail, called deadenylation, is the first and the most crucial step in the process of mRNA degradation. Poly (A)-specific ribonuclease (PARN) is one such enzyme that catalyses the process of deadenylation. Although PARN has been primarily known as the regulator of the mRNA stability, recent evidence clearly suggests several other functions of PARN, including a role in embryogenesis, oocyte maturation, cell-cycle progression, telomere biology, non-coding RNA maturation and ribosome biogenesis. Also, deregulated PARN activity is shown to be a hallmark of specific disease conditions. Pathogenic variants in the PARN gene have been observed in various cancers and inherited bone marrow failure syndromes. The focus in this review is to highlight the emerging functions of PARN, particularly in the context of human diseases.
在真核细胞中，mRNA 的合成和降解之间的平衡决定了其稳定状态。聚腺苷酸尾（poly(A) tail）上腺苷酸残基的去除，即去腺苷酸化，是 mRNA 降解过程中的第一步，也是最关键的一步。聚（A）特异性核糖核酸酶（PARN）是一种能够催化去腺苷酸化过程的酶。尽管 PARN 主要被认为是调节 mRNA 稳定性的酶，但最近的证据清楚地表明 PARN 具有多种其他功能，包括在胚胎发生、卵母细胞成熟、细胞周期进程、端粒生物学、非编码 RNA 成熟和核糖体生物发生中的作用。此外，PARN 活性失调被证明是特定疾病状况的特征。PARN 基因中的致病变异已在各种癌症和遗传性骨髓衰竭综合征中被观察到。本综述的重点是强调 PARN 的新兴功能，特别是在人类疾病方面。
