title: Protein cofactor competition regulates the action of a multifunctional RNA helicase in different pathways.
abstract: A rapidly increasing number of RNA helicases are implicated in several distinct cellular processes, however, the modes of regulation of multifunctional RNA helicases and their recruitment to different target complexes have remained unknown. Here, we show that the distribution of the multifunctional DEAH-box RNA helicase Prp43 between its diverse cellular functions can be regulated by the interplay of its G-patch protein cofactors. We identify the orphan G-patch protein Cmg1 (YLR271W) as a novel cofactor of Prp43 and show that it stimulates the RNA binding and ATPase activity of the helicase. Interestingly, Cmg1 localizes to the cytoplasm and to the intermembrane space of mitochondria and its overexpression promotes apoptosis. Furthermore, our data reveal that different G-patch protein cofactors compete for interaction with Prp43. Changes in the expression levels of Prp43-interacting G-patch proteins modulate the cellular localization of Prp43 and G-patch protein overexpression causes accumulation of the helicase in the cytoplasm or nucleoplasm. Overexpression of several G-patch proteins also leads to defects in ribosome biogenesis that are consistent with withdrawal of the helicase from this pathway. Together, these findings suggest that the availability of cofactors and the sequestering of the helicase are means to regulate the activity of multifunctional RNA helicases and their distribution between different cellular processes.
authors.affiliation: a Institute for Molecular Biology, Georg-August University , Goettingen , Germany.
authors.forename: Annika U
authors.initials: AU
authors.lastname: Heininger
authors.affiliation: a Institute for Molecular Biology, Georg-August University , Goettingen , Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hackert
authors.affiliation: b Institute for Physical Chemistry, University of Muenster , Muenster , Germany.
authors.forename: Alexandra Z
authors.initials: AZ
authors.lastname: Andreou
authors.affiliation: c Max-Planck-Institute for Biophysical Chemistry , Goettingen , Germany.
authors.forename: Kum-Loong
authors.initials: KL
authors.lastname: Boon
authors.affiliation: a Institute for Molecular Biology, Georg-August University , Goettingen , Germany.
authors.forename: Indira
authors.initials: I
authors.lastname: Memet
authors.affiliation: d III. Institute of Physics-Biophysics, Georg-August University , Goettingen , Germany.
authors.forename: Mira
authors.initials: M
authors.lastname: Prior
authors.affiliation: a Institute for Molecular Biology, Georg-August University , Goettingen , Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Clancy
authors.affiliation: e Institute of Cellular Biochemistry, Georg-August University , Goettingen , Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: c Max-Planck-Institute for Biophysical Chemistry , Goettingen , Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.affiliation: f Institute for Molecular Biosciences, Goethe University , Frankfurt , Germany.
authors.forename: Enrico
authors.initials: E
authors.lastname: Schleiff
authors.affiliation: a Institute for Molecular Biology, Georg-August University , Goettingen , Germany.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Sloan
authors.affiliation: e Institute of Cellular Biochemistry, Georg-August University , Goettingen , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Deckers
authors.affiliation: c Max-Planck-Institute for Biophysical Chemistry , Goettingen , Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lührmann
authors.affiliation: d III. Institute of Physics-Biophysics, Georg-August University , Goettingen , Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Enderlein
authors.affiliation: b Institute for Physical Chemistry, University of Muenster , Muenster , Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Klostermeier
authors.affiliation: c Max-Planck-Institute for Biophysical Chemistry , Goettingen , Germany.|e Institute of Cellular Biochemistry, Georg-August University , Goettingen , Germany.|g Goettingen Center for Molecular Biosciences, Georg-August-University , Goettingen , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.affiliation: a Institute for Molecular Biology, Georg-August University , Goettingen , Germany.|g Goettingen Center for Molecular Biosciences, Georg-August-University , Goettingen , Germany.
authors.forename: Markus T
authors.initials: MT
authors.lastname: Bohnsack
mesh_terms: D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051336:Mitochondrial Membranes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C109034:PRP43 protein, S cerevisiae; D053487:DEAD-box RNA Helicases
keywords: G-patch protein; RNA helicase; protein cofactor; ribosome; splicing
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