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Translation mediated by the nuclear cap-binding complex is confined to the perinuclear region via a CTIF–DDX19B interaction

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Park Yeonkyoung, Park Joori, Hwang Hyun Jung, Kim Leehyeon, Jeong Kwon, Song Hyun Kyu, Rufener Simone C, Mühlemann Oliver, Kim Yoon Ki,
Project Towards understanding mechanism and physiological role of nonsense-mediated mRNA decay (NMD)
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Original article (peer-reviewed)

Journal Nucleic Acids Research
Volume (Issue) 49(14)
Page(s) 8261 - 8276
Title of proceedings Nucleic Acids Research
DOI 10.1093/nar/gkab579

Open Access

URL http://doi.org/10.1093/nar/gkab579
Type of Open Access Publisher (Gold Open Access)

Abstract

AbstractNewly synthesized mRNA is translated during its export through the nuclear pore complex, when its 5′-cap structure is still bound by the nuclear cap-binding complex (CBC), a heterodimer of cap-binding protein (CBP) 80 and CBP20. Despite its critical role in mRNA surveillance, the mechanism by which CBC-dependent translation (CT) is regulated remains unknown. Here, we demonstrate that the CT initiation factor (CTIF) is tethered in a translationally incompetent manner to the perinuclear region by the DEAD-box helicase 19B (DDX19B). DDX19B hands over CTIF to CBP80, which is associated with the 5′-cap of a newly exported mRNA. The resulting CBP80–CTIF complex then initiates CT in the perinuclear region. We also show that impeding the interaction between CTIF and DDX19B leads to uncontrolled CT throughout the cytosol, consequently dysregulating nonsense-mediated mRNA decay. Altogether, our data provide molecular evidence supporting the importance of tight control of local translation in the perinuclear region.
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