mRNA decay is required for many biological events, and dysregulation of the mechanism leads to disorders, including cancer, neurodegenerative diseases and diabetes. A shortening of poly(A) tails (deadenylation) triggers mRNA degradation, that is mainly mediated by the CCR4-NOT complex.
Liver development involves dramatic gene expression change mediated by transcriptional and post-transcriptional control. We generated mice lacking a Cnot3 gene, encoding an essential subunit of the CCR4-NOT complex, in liver from a neonatal stage (Cnot3-LKO mice). Hepatocyte death and inflammation were observed in the livers of Cnot3-LKO mice. Gene expression analysis showed increased expression of immune response-related, cell cycle-regulating, and immature liver genes in the livers of Cnot3-LKO mice. In contrast, genes, which are relevant to liver functions, such as oxidation-reduction and lipid metabolism, decreased, indicating impaired liver functional maturation. Highly expressed mRNAs possessed elongated poly(A) tails and were stabilized in the livers of Cnot3-LKO mice. Similar results were obtained when we suppressed the CCR4-NOT complex in adult mouse liver. These data suggest that the CCR4-NOT complex-mediated mRNA decay plays a critical role in liver maturation and function, providing novel insights into tissue development and homeostasis.
Dr. Toru Suzuki is a Senior Researcher at RIKEN, Center for Integrative Medical Sciences from 2016. Main research interests are roles of posttranscriptional mechanisms in biological processes.
He received Ph.D. from University of Tokyo in 2001. He became Research Associate at Division of Oncology, Department of Cancer Biology, Institute of Medical Sciences, University of Tokyo and did research to 2012. He moved to Okinawa Institute of Science and Technology Graduate University as a Staff Scientist at Cell Signal Unit in 2012 and worked until 2016.