title: The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality.
abstract: A major determinant of mRNA half-life is the codon-dependent rate of translational elongation. How the processes of translational elongation and mRNA decay communicate is unclear. Here, we establish that the DEAD-box protein Dhh1p is a sensor of codon optimality that targets an mRNA for decay. First, we find mRNAs whose translation elongation rate is slowed by inclusion of non-optimal codons are specifically degraded in a Dhh1p-dependent manner. Biochemical experiments show Dhh1p is preferentially associated with mRNAs with suboptimal codon choice. We find these effects on mRNA decay are sensitive to the number of slow-moving ribosomes on an mRNA. Moreover, we find Dhh1p overexpression leads to the accumulation of ribosomes specifically on mRNAs (and even codons) of low codon optimality. Lastly, Dhh1p physically interacts with ribosomes in vivo. Together, these data argue that Dhh1p is a sensor for ribosome speed, targeting an mRNA for repression and subsequent decay.
authors.affiliation: Program in Molecular Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Radhakrishnan
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Ying-Hsin
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Martin
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Najwa
authors.initials: N
authors.lastname: Alhusaini
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address: ragreen@jhmi.edu.
authors.forename: Rachel
authors.initials: R
authors.lastname: Green
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: jmc71@case.edu.
authors.forename: Jeff
authors.initials: J
authors.lastname: Coller
mesh_terms: D003062:Codon / Q000235:genetics / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D006207:Half-Life; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D003062:Codon; D012333:RNA, Messenger; D053487:DEAD-box RNA Helicases