Journal
NUCLEIC ACIDS RESEARCH
Volume 49, Issue 14, Pages 8261-8276Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab579
Keywords
-
Categories
Funding
- Korean government (Ministry of Science, ICT and Future Planning) [NRF-2015R1A3A2033665, NRF-2018R1A5A1024261]
- Korea University
- National Research Foundation (NRF) of Korea [NRF-2015R1A3A2033665]
Ask authors/readers for more resources
It has been demonstrated that CTIF is tethered to the perinuclear region by DDX19B in a translationally incompetent manner, and then handed over to CBP80, which is associated with the 5'-cap of newly exported mRNA, initiating CBC-dependent translation in the perinuclear region. Disrupting the interaction between CTIF and DDX19B leads to uncontrolled translation in the cytosol, ultimately affecting nonsense-mediated mRNA decay. This highlights the importance of tight control of local translation in the perinuclear region.
Newly 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available