title: A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay.
abstract: In eukaryotes, a surveillance mechanism known as nonsense-mediated decay (NMD) degrades the mRNA when a premature-termination codon (PTC) is present. NMD requires translation to read the frame of the mRNA and detect the PTC. During pre-mRNA splicing, the exon-exon junction complex (EJC) is recruited to a region 20-24 nt upstream of the exon junction on the mature mRNA. The presence of a PTC upstream from the EJC elicits NMD. Eukaryotic initiation factor 4A (eIF4A) III is a nuclear protein that interacts physically or functionally with translation initiation factors eIF4G and eIF4B, respectively, and shares strikingly high identity with the initiation factors eIF4AI/II. Here we show that siRNA against eIF4AIII, but not against eIF4AI/II, inhibits NMD. Moreover, eIF4AIII, but not eIF4AI, is specifically recruited to the EJC during splicing. The observations that eIF4AIII is loaded onto the mRNA during splicing in the nucleus, has properties related to a translation initiation factor, and functions in NMD raises the possibility that eIF4AIII substitutes for eIF4AI/II during NMD.
authors.affiliation: Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ferraiuolo
authors.forename: Chung-Sheng
authors.initials: CS
authors.lastname: Lee
authors.forename: Lian Wee
authors.initials: LW
authors.lastname: Ler
authors.forename: Jeanne L
authors.initials: JL
authors.lastname: Hsu
authors.forename: Mauro
authors.initials: M
authors.lastname: Costa-Mattioli
authors.forename: Ming-Juan
authors.initials: MJ
authors.lastname: Luo
authors.forename: Robin
authors.initials: R
authors.lastname: Reed
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000818:Animals; D018389:Codon, Nonsense / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009865:Oocytes / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D012326:RNA Splicing / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering; D014981:Xenopus
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D039601:Eukaryotic Initiation Factor-4A