Integrated Deadenylase Genetic Association Network and Transcriptome Analysis in Thoracic Carcinomas

Abstract

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.

RNA deadenylation complexes in development and diseases

“…CNOT6L was reported to alter the level of p27 Kip1 , known as a tumor suppressor, but also functions as an oncogene by promoting metastasis (Morita et al 2007). RNA deadenylases have been found to target unique subsets of mRNAs in a cell type specific-manner (Kyritsis et al 2022).…”