MassIVE MSV000098386

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Multivalent Interactions with CCR4-NOT and PABPC1 Determine mRNA Repression Efficiency by Tristetraprolin

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Description

Tristetraprolin family of proteins regulate mRNA stability by binding to specific AU-rich elements in transcripts. This binding promotes the shortening of the mRNA poly(A) tail, or deadenylation, initiating mRNA degradation. The CCR4-NOT complex plays a central role in deadenylation, while the cytoplasmic poly(A)-binding protein PABPC1 typically protects mRNAs from decay. Here, we investigate how tristetraprolin interacts with CCR4-NOT and PABPC1 to control mRNA stability. Using purified proteins and in vitro assays, we find that tristetraprolin engages CCR4-NOT through multiple interaction sites and promotes its activity, emphasizing the importance of multivalent binding for efficient deadenylation. Phosphorylation of tristetraprolin does not affect its interaction with CCR4-NOT or its deadenylation activity, but is essential for tristetraprolin binding to PABPC1. We propose that tristetraprolin promotes the processive deadenylation activity of CCR4-NOT on mRNAs containing AU-rich elements, with phosphorylation-dependent interactions with PABPC1 potentially enhancing deadenylation and promoting regulated mRNA decay. [doi:10.25345/C5FQ9QJ40] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Tristetraprolin (TTP), CCR4-NOT complex, PABPC1, mRNA deadenylation, phosphorylation, multivalent interactions, AU-rich elements (AREs), mRNA stability, RNA-binding proteins, post-translational modifications. ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Eugene Valkov, NIH/NCI, United States
Submitting User: ronholes7059
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