Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, 415 00 Larissa, Greece.
Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Biopolis, 411 10 Larissa, Greece.
Molecules. 2022 May 12;27(10):3102. doi: 10.3390/molecules27103102.
The poly(A) tail at the 3' end of mRNAs determines their stability, translational efficiency, and fate. The shortening of the poly(A) tail, and its efficient removal, triggers the degradation of mRNAs, thus, regulating gene expression. The process is catalyzed by a family of enzymes, known as deadenylases. As the dysregulation of gene expression is a hallmark of cancer, understanding the role of deadenylases has gained additional interest. Herein, the genetic association network shows that CNOT6 and CNOT7 are the most prevalent and most interconnected nodes in the equilibrated diagram. Subsequent silencing and transcriptomic analysis identifies transcripts possibly regulated by specific deadenylases. Furthermore, several gene ontologies are enriched by common deregulated genes. Given the potential concerted action and overlapping functions of deadenylases, we examined the effect of silencing a deadenylase on the remaining ones. Our results suggest that specific deadenylases target unique subsets of mRNAs, whilst at the same time, multiple deadenylases may affect the same mRNAs with overlapping functions.
mRNA 3' 端的多聚 (A) 尾决定了它们的稳定性、翻译效率和命运。多聚 (A) 尾的缩短及其有效去除会触发 mRNA 的降解，从而调节基因表达。该过程由一系列称为脱腺苷酶的酶催化。由于基因表达失调是癌症的一个标志，因此，脱腺苷酶的作用引起了更多的关注。在此，遗传关联网络显示，CNOT6 和 CNOT7 是平衡图中最常见和相互连接最多的节点。随后的沉默和转录组分析确定了可能受特定脱腺苷酶调节的转录本。此外，几个基因本体论被常见的失调基因所富集。鉴于脱腺苷酶的潜在协同作用和重叠功能，我们检查了沉默一种脱腺苷酶对其余脱腺苷酶的影响。我们的结果表明，特定的脱腺苷酶靶向独特的 mRNA 子集，而同时，多种脱腺苷酶可能具有重叠功能而影响相同的 mRNA。
