The CCR4-NOT complex maintains liver homeostasis through mRNA deadenylation.

Autor:	Takahashi A; Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan., Suzuki T; Laboratory for Immunogenetics, Center for Integrative Medical Sciences, RIKEN, Yokohama City, Kanagawa, Japan toru.suzuki.ff@riken.jp., Soeda S; Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan., Takaoka S; Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan., Kobori S; Nucleic Acid Chemistry and Engineering Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan., Yamaguchi T; Department of Biochemistry and Metabolic Science, Graduate School of Medicine, Akita University, Akita, Japan., Mohamed HMA; Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan., Yanagiya A; Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan., Abe T; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan., Shigeta M; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan., Furuta Y; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan., Kuba K; Department of Biochemistry and Metabolic Science, Graduate School of Medicine, Akita University, Akita, Japan., Yamamoto T; Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan tadashi.yamamoto@oist.jp.; Laboratory for Immunogenetics, Center for Integrative Medical Sciences, RIKEN, Yokohama City, Kanagawa, Japan.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2020 Apr 01; Vol. 3 (5). Date of Electronic Publication: 2020 Apr 01 (Print Publication: 2020).
DOI:	10.26508/lsa.201900494
Abstrakt:	The biological significance of deadenylation in global gene expression is not fully understood. Here, we show that the CCR4-NOT deadenylase complex maintains expression of mRNAs, such as those encoding transcription factors, cell cycle regulators, DNA damage response-related proteins, and metabolic enzymes, at appropriate levels in the liver. Liver-specific disruption of Cnot1 , encoding a scaffold subunit of the CCR4-NOT complex, leads to increased levels of mRNAs for transcription factors, cell cycle regulators, and DNA damage response-related proteins because of reduced deadenylation and stabilization of these mRNAs. CNOT1 suppression also results in an increase of immature, unspliced mRNAs (pre-mRNAs) for apoptosis-related and inflammation-related genes and promotes RNA polymerase II loading on their promoter regions. In contrast, mRNAs encoding metabolic enzymes become less abundant, concomitant with decreased levels of these pre-mRNAs. Lethal hepatitis develops concomitantly with abnormal mRNA expression. Mechanistically, the CCR4-NOT complex targets and destabilizes mRNAs mainly through its association with Argonaute 2 (AGO2) and butyrate response factor 1 (BRF1) in the liver. Therefore, the CCR4-NOT complex contributes to liver homeostasis by modulating the liver transcriptome through mRNA deadenylation. (© 2020 Takahashi et al.)
Databáze:	MEDLINE
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