DEAD box RNA helicases act as nucleotide exchange factors for casein kinase 2

Fatti, Edoardo; Hirth, Alexander; Svorinic, Andrea; Günther, Matthias; Stier, Günter; Cruciat, Cristina-Maria; Acebrón, Sergio P.; Papageorgiou, Dimitris; Sinning, Irmgard; Krijgsveld, Jeroen; Höfer, Thomas; Niehrs, Christof

doi:10.1126/scisignal.abp8923

Cited by 2 publications

References 51 publications

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Substrate Specificities of DDX1: A Human DEAD-box protein

Moore,

Berhie,

Weislow

et al. 2024

Preprint

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DDX1 is a human protein which belongs to the DEAD-box protein family of enzymes and is involved in various stages of RNA metabolism from transcription to decay. Many members of the DEAD-box family of enzymes use the energy of ATP binding and hydrolysis to perform their cellular functions. On the other hand, a few members of the DEAD-box family of enzymes bind and/or hydrolyze other nucleotides in addition to ATP. Furthermore, the ATPase activity of DEAD-box family members is stimulated differently by nucleic acids of various structures. The identity of the nucleotides that the DDX1 hydrolyzes and the structure of the nucleic acids upon which it acts in the cell remain largely unknown. Identifying the DDX1 protein’sin vitrosubstrates is important for deciphering the molecular roles of DDX1 in cells. Here we identify the nucleic acid sequences and structures supporting the nucleotide hydrolysis activity of DDX1 and its nucleotide specificity. Our data demonstrate that the DDX1 protein hydrolyzes only ATP and deoxy-ATP in the presence of RNA. The ATP hydrolysis activity of DDX1 is stimulated by multiple molecules: single-stranded RNA molecules as short as ten nucleotides, a blunt-ended double-stranded RNA molecule, a hybrid of a double-stranded DNA-RNA molecule, and a single-stranded DNA molecule. Under our experimental conditions, the single-stranded DNA molecule stimulates the ATPase activity of DDX1 at a significantly reduced extent when compared to the other investigated RNA constructs or the hybrid double-stranded DNA/RNA molecule.

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Substrate Specificities of DDX1: A Human DEAD-box protein

Moore,

Berhie,

Weislow

et al. 2024

Preprint

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DEAD box RNA helicases are pervasive protein kinase interactors and activators

Hirth,

Fatti,

Netz

et al. 2024

Genome Res.

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DEAD box (DDX) RNA helicases are a large family of ATPases, many of which have unknown functions. There is emerging evidence that besides their role in RNA biology, DDX proteins may stimulate protein kinases. To investigate if protein kinase–DDX interaction is a more widespread phenomenon, we conducted three orthogonal large-scale screens, including proteomics analysis with 32 RNA helicases, protein array profiling, and kinome-wide in vitro kinase assays. We retrieved Ser/Thr protein kinases as prominent interactors of RNA helicases and report hundreds of binary interactions. We identified members of ten protein kinase families, which bind to, and are stimulated by, DDX proteins, including CDK, CK1, CK2, DYRK, MARK, NEK, PRKC, SRPK, STE7/MAP2K, and STE20/PAK family members. We identified MARK1 in all screens and validated that DDX proteins accelerate the MARK1 catalytic rate. These findings indicate pervasive interactions between protein kinases and DEAD box RNA helicases, and provide a rich resource to explore their regulatory relationships.

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DEAD box RNA helicases act as nucleotide exchange factors for casein kinase 2

Cited by 2 publications

References 51 publications

Substrate Specificities of DDX1: A Human DEAD-box protein

Substrate Specificities of DDX1: A Human DEAD-box protein

DEAD box RNA helicases are pervasive protein kinase interactors and activators

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