Inositol hexakisphosphate kinase 1 (IP6K1) is a small molecule kinase that catalyzes the conversion of the inositol phosphate IP6 to 5-IP7. We show that IP6K1 acts independent of its catalytic activity to upregulate the formation of processing bodies (P-bodies), which are cytoplasmic ribonucleoprotein granules that store translationally repressed mRNA. IP6K1 does not localize to P-bodies, but instead binds to ribosomes, where it interacts with the mRNA decapping complex - the scaffold protein EDC4, activator proteins DCP1A/B, decapping enzyme DCP2, and RNA helicase DDX6. Along with its partner 4E-T, DDX6 is known to nucleate protein-protein interactions on the 5’ mRNA cap to facilitate P-body formation. IP6K1 binds the translation initiation complex eIF4F on the mRNA cap, augmenting the interaction of DDX6 with 4E-T and the cap binding protein eIF4E. Cells with reduced IP6K1 show downregulated microRNA-mediated translational suppression and increased stability of DCP2-regulated transcripts. Our findings unveil IP6K1 as a novel facilitator of proteome remodelling on the mRNA cap, tipping the balance in favour of translational repression over initiation, thus leading to P-body assembly.
IP6K1 upregulates the formation of processing bodies by influencing protein-protein interactions on the mRNA cap
- Award Group:
- Funder(s): Human Frontier Science Program
- Award Id(s): RGP0025/2016
- Funder(s):
- Award Group:
- Funder(s): Department of Biotechnology, Ministry of Science and Technology, India
- Award Id(s): BT/PR29960/BRB/10/1762/2019
- Funder(s):
- Award Group:
- Funder(s): Science and Engineering Research Board
- Award Id(s): CRG/2019/002597
- Funder(s):
- Award Group:
- Funder(s): Centre for DNA Fingerprinting and Diagnostics
- Funder(s):
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Akruti Shah, Rashna Bhandari; IP6K1 upregulates the formation of processing bodies by influencing protein-protein interactions on the mRNA cap. J Cell Sci 2021; jcs.259117. doi: https://doi.org/10.1242/jcs.259117
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