EIF4A RNA Helicase Associates with Cyclin-Dependent Protein Kinase A in Proliferating Cells and Is Modulated by Phosphorylation  . Issue 1 (7th July 2016)

• Record Type: Journal Article
• Authors: Bush, Maxwell S.; Pierrat, Olivier; Nibau, Candida; Mikitova, Veronika; Zheng, Tao; Corke, Fiona M. K.; Vlachonasios, Konstantinos; Mayberry, Laura K.; Browning, Karen S.; Doonan, John H.
• Is Part Of: Plant physiology. Volume 172:Issue 1(2016)
• Page Start: 128
• Page End: 140
• Publication Date: 2016-07-07
• Subjects: Plant physiology -- Periodicals; Botany -- Periodicals; Periodicals; Electronic journals; 571.2
• DOI: 10.1104/pp.16.00435
• Languages: English
• ISSNs: 0032-0889

Abstract

Abstract : CDKA phosphorylation of the RNA helicase, eIF4A, is restricted to proliferating cells and could provide a mechanism that inhibits translation and cell growth in a cell cycle-dependent manner. Abstract: Eukaryotic initiation factor 4A (eIF4A) is a highly conserved RNA-stimulated ATPase and helicase involved in the initiation of messenger RNA translation. Previously, we found that eIF4A interacts with cyclin-dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. Here, we show that this interaction occurs only in proliferating cells where the two proteins coassociate with 5′-cap-binding protein complexes, eIF4F or the plant-specific eIFiso4F. CDKA phosphorylates eIF4A on a conserved threonine residue (threonine-164) within the RNA-binding motif 1b TPGR. In vivo, a phospho-null (APGR) variant of the Arabidopsis ( Arabidopsis thaliana ) eIF4A1 protein retains the ability to functionally complement a mutant ( eif4a1 ) plant line lacking eIF4A1, whereas a phosphomimetic (EPGR) variant fails to complement. The phospho-null variant (APGR) rescues the slow growth rate of roots and rosettes, together with the ovule-abortion and late-flowering phenotypes. In vitro, wild-type recombinant eIF4A1 and its phospho-null variant both support translation in cell-free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and also was deficient in ATP hydrolysis and helicase activity. These observations suggest a mechanism whereby CDK phosphorylation has the potential to down-regulate eIF4A activity and thereby affect translation.