title: The DHX33 RNA Helicase Promotes mRNA Translation Initiation.
abstract: DEAD/DEAH box RNA helicases play essential roles in numerous RNA metabolic processes, such as mRNA translation, pre-mRNA splicing, ribosome biogenesis, and double-stranded RNA sensing. Herein we show that a recently characterized DEAD/DEAH box RNA helicase, DHX33, promotes mRNA translation initiation. We isolated intact DHX33 protein/RNA complexes in cells and identified several ribosomal proteins, translation factors, and mRNAs. Reduction of DHX33 protein levels markedly reduced polyribosome formation and caused the global inhibition of mRNA translation that was rescued with wild-type DHX33 but not helicase-defective DHX33. Moreover, we observed an accumulation of mRNA complexes with the 80S ribosome in the absence of functional DHX33, consistent with a stalling in initiation, and DHX33 more preferentially promoted structured mRNA translation. We conclude that DHX33 functions to promote elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation. Our results reveal a newly recognized function of DHX33 in mRNA translation initiation, further solidifying its central role in promoting cell growth and proliferation.
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, People's Republic of China zhangyd@sustc.edu.cn jweber@dom.wustl.edu.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: You
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Xingshun
authors.initials: X
authors.lastname: Wang
authors.affiliation: ICCE Institute, Department of Internal Medicine, Division of Molecular Oncology, Washington University School of Medicine, St. Louis, Missouri, USA zhangyd@sustc.edu.cn jweber@dom.wustl.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Weber
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics; D005260:Female; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D011132:Polyribosomes / Q000235:genetics*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C534219:DHX29 protein, human; D039601:Eukaryotic Initiation Factor-4A; C568925:DHX33 protein, human; C403493:EIF4A3 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases