Integrated Deadenylase Genetic Association Network and Transcriptome Analysis in Thoracic Carcinomas

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.

Automated summary

The poly(A) tail at the 3' end of mRNAs plays a crucial role in their stability, translational efficiency, and degradation. Deadenylases are a family of enzymes that catalyze the shortening and removal of the poly(A) tail, thus regulating gene expression. Dysregulation of gene expression is closely associated with cancer, making the study of deadenylases essential. In this study, we found that CNOT6 and CNOT7 are the most prevalent and interconnected deadenylases. Silencing specific deadenylases affects the regulation of specific transcripts, while multiple deadenylases can have overlapping functions in regulating the same transcripts.