microRNA-induced translational control of antiviral immunity by the cap-binding protein 4EHP.

Autor:	Zhang X; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Chapat C; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Wang P; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Choi JH; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Li Q; Meakins-Christie Laboratories and Respiratory Division, McGill University, Montreal, QC H4A 3J1, Canada., Luo J; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Wiebe S; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Kim SH; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Robichaud N; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Karam IF; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Dai D; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Hackett AP; Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK., Lin R; Lady Davis Institute, Department of Medicine, McGill University, Montreal, QC H3T 1E2, Canada., Alain T; Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 5B2, Canada., Yang L; Lady Davis Institute, Department of Medicine, McGill University, Montreal, QC H3T 1E2, Canada. Electronic address: longyangrich@hotmail.com., Jafarnejad SM; Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK. Electronic address: sm.jafarnejad@qub.ac.uk., Sonenberg N; Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address: nahum.sonenberg@mcgill.ca.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2021 Mar 18; Vol. 81 (6), pp. 1187-1199.e5. Date of Electronic Publication: 2021 Feb 12.
DOI:	10.1016/j.molcel.2021.01.030
Abstrakt:	Type I interferons (IFNs) are critical cytokines in the host defense against invading pathogens. Sustained production of IFNs, however, is detrimental to the host, as it provokes autoimmune diseases. Thus, the expression of IFNs is tightly controlled. We report that the mRNA 5' cap-binding protein 4EHP plays a key role in regulating type I IFN concomitant with controlling virus replication, both in vitro and in vivo. Mechanistically, 4EHP suppresses IFN-β production by effecting the miR-34a-induced translational silencing of Ifnb1 mRNA. miR-34a is upregulated by both RNA virus infection and IFN-β induction, prompting a negative feedback regulatory mechanism that represses IFN-β expression via 4EHP. These findings demonstrate the direct involvement of 4EHP in virus-induced host response, underscoring a critical translational silencing mechanism mediated by 4EHP and miR-34a to impede sustained IFN production. This study highlights an intrinsic regulatory function for miRNA and the translation machinery in maintaining host homeostasis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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