RNA deadenylation complexes in development and diseases

• Published in: Biochemistry and cell biology Vol. 101; no. 2; pp. 131 - 147
• Main Authors: Liu, Yilin, Ramkumar, Niveditha, Vu, Ly P
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.03.2023; Canadian Science Publishing NRC Research Press
• Subjects: Analysis; Cell differentiation; Coronary artery disease; Decay; Exoribonucleases - genetics; Exoribonucleases - metabolism; Gene expression; Gene Expression Regulation; Gene regulation; Heart diseases; Humans; Life cycles; Messenger RNA; Methods; mRNA turnover; Neurodevelopmental disorders; Polyadenylation; Post-transcription; Regulatory proteins; Ribonucleic acid; RNA; RNA - genetics; RNA, Messenger - metabolism; Transcription Factors - metabolism; Translation; Canada; RNA deadenylation; RNA decay; PAN complex; post-transcriptional gene expression; poly(A) tail; CCR4-NOT complex
• ISSN: 0829-8211; 1208-6002
• DOI: 10.1139/bcb-2022-0325

RNA deadenylation, the process of shortening of the 3' poly(A) tail of an RNA molecule, is one of the key steps of post-transcriptional regulation of gene expression in eukaryotic cells. PAN2/3 and CCR4-NOT (CNOT) are the two dominant RNA deadenylation complexes, which play central roles in mediating mRNA decay and translation. While degradation is the final fate of virtually all RNAs in their life cycles, selection of RNA targets as well as control of the rate and timing of RNA decay, in coordination with other molecular pathways, including translation, can be modulated in certain contexts. Such regulation influences cell growth, proliferation, and differentiation at the cellular level; and contributes to establish polarity and regulate signaling at the tissue level. Dysregulation of deadenylation processes have also been implicated in human diseases ranging from cardiac diseases and neurodevelopmental disorders to cancers. In this review, we will discuss mechanisms of gene expression control mediated by the RNA deadenylation complexes and highlight relevant evidence supporting the emerging roles of RNA deadenylation and its regulatory proteins during development and in diseases. A systemic understanding of these mechanisms will be a critical foundation for development of effective strategies to therapeutically target them.