Department of Microbiology and Physiological Systems
Amino Acids, Peptides, and Proteins | Fungi | Genetic Phenomena | Genetics and Genomics | Nucleic Acids, Nucleotides, and Nucleosides
Scd6 protein family members are evolutionarily conserved components of translationally silent mRNA granules. Yeast Scd6 interacts with Dcp2 and Dhh1, respectively a subunit and a regulator of the mRNA decapping enzyme, and also associates with translation initiation factor eIF4G to inhibit translation in cell extracts. However, the role of Scd6 in mRNA turnover and translational repression in vivo is unclear. We demonstrate that tethering Scd6 to a GFP reporter mRNA reduces mRNA abundance via Dcp2 and suppresses reporter mRNA translation via Dhh1. Thus, in a dcp2Delta mutant, tethered Scd6 reduces GFP protein expression with little effect on mRNA abundance, whereas tethered Scd6 has no impact on GFP protein or mRNA expression in a dcp2Delta dhh1Delta double mutant. The conserved LSm domain of Scd6 is required for translational repression and mRNA turnover by tethered Scd6. Both functions are enhanced in a ccr4Delta mutant, suggesting that the deadenylase function of Ccr4-Not complex interferes with a more efficient repression pathway enlisted by Scd6. Ribosome profiling and RNA-Seq analysis of scd6Delta and dhh1Delta mutants suggests that Scd6 cooperates with Dhh1 in translational repression and turnover of particular native mRNAs, with both processes dependent on Dcp2. Our results suggest that Scd6 can (i) recruit Dhh1 to confer translational repression and (ii) activate mRNA decapping by Dcp2 with attendant degradation of specific mRNAs in vivo, in a manner dependent on the Scd6 LSm domain and modulated by Ccr4.
Messenger RNA, Protein translation, Protein expression, Ribosomes, Statistical data, Plasmid construction, Translation initiation, Yeast
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DOI of Published Version
PLoS Genet. 2018 Dec 7;14(12):e1007806. doi: 10.1371/journal.pgen.1007806. eCollection 2018 Dec. Link to article on publisher's site
Zeidan, Quira; He, Feng; Zhang, Fan; Zhang, Hongen; Jacobson, Allan; and Hinnebusch, Alan G., "Conserved mRNA-granule component Scd6 targets Dhh1 to repress translation initiation and activates Dcp2-mediated mRNA decay in vivo" (2018). Open Access Articles. 3690.
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