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Published on: July 10, 2019
MARVELD1 Inhibits Nonsense-Mediated RNA Decay by Repressing Serine Phosphorylation of UPF1
1School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Abstract:
We have observed low expression levels of MARVELD1, a novel tumor repressor, in multiple tumors; however, its function in normal cells has not been explored. We recently reported that MARVELD1 interacts with importin β1, which plays an important role in nonsense-mediated RNA decay(NMD). Here, we demonstrate that MARVELD1 substantially inhibits nonsense-mediated RNA decay by decreasing the pioneer round of translation but not steady-state translation, and we identify MARVELD1 as an important component of the molecular machinery containing UPF1 and Y14. Furthermore, we determined the specific regions of MARVELD1 and UPF1 responsible for their interaction. We also showed that MARVELD1 promotes the dissociation of SMG1 from UPF1, resulting in the repression of serine phosphorylation of UPF1, and subsequently blocks the recruitment of SMG5, which is required for ensuing SMG5-mediated exonucleolytic decay. Our observations provide molecular insight into the potential function of MARVELD1 in nonsense-mediated RNA decay.
Insights
MARVELD1, a tumor suppressor, inhibits nonsense-mediated RNA decay (NMD) by regulating translation initiation. This study reveals MARVELD1
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- MARVELD1 is a novel tumor repressor with low expression in tumors.
- Its function in normal cells and its role in RNA regulation were previously unexplored.
- MARVELD1 interacts with importin β1, a key factor in nonsense-mediated RNA decay (NMD).
Purpose of the Study:
- To elucidate the function of MARVELD1 in normal cells.
- To investigate the role of MARVELD1 in nonsense-mediated RNA decay (NMD).
- To identify the molecular mechanisms by which MARVELD1 regulates NMD.
Main Methods:
- Investigated MARVELD1's effect on the pioneer round of translation and steady-state translation.
- Identified MARVELD1 as part of the UPF1 and Y14 molecular machinery.
- Determined the interaction regions between MARVELD1 and UPF1.
- Assessed the impact of MARVELD1 on UPF1 phosphorylation and SMG5 recruitment.
Main Results:
- MARVELD1 significantly inhibits NMD by reducing the pioneer round of translation.
- MARVELD1 is a component of the UPF1 and Y14 complex involved in NMD.
- MARVELD1 interaction regions with UPF1 were identified.
- MARVELD1 disrupts SMG1-UPF1 interaction, inhibiting UPF1 phosphorylation and SMG5-mediated decay.
Conclusions:
- MARVELD1 acts as a crucial regulator of nonsense-mediated RNA decay (NMD).
- MARVELD1 inhibits NMD by modulating translation initiation and protein complex formation.
- These findings offer molecular insights into MARVELD1's function in RNA surveillance and cancer.
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