eIF4A3 is a novel component of the exon junction complex.
The exon junction complex (EJC) is a protein complex that assembles near exon-exon junctions of mRNAs as a result of splicing. EJC proteins play important roles in postsplicing events including mRNA export, cytoplasmic localization, and nonsense-mediated decay. Recent evidence suggests that mRNA translation is also influenced by the splicing history of the transcript. Here we identify eIF4A3, a DEAD-box RNA helicase and a member of the eIF4A family of translation initiation factors, as a novel component of the EJC. We show that eIF4A3 associates preferentially with nuclear complexes containing the EJC proteins magoh and Y14. Furthermore, eIF4A3, but not the highly related eIF4A1 or eIF4A2, preferentially associates with spliced mRNA. In vitro splicing and mapping experiments demonstrate that eIF4A3 binds mRNAs at the position of the EJC. Using monoclonal antibodies, we show that eIF4A3 is found in the nucleus whereas eIF4A1 and eIF4A2 are found in the cytoplasm. Thus, eIF4A3 likely provides a splicing-dependent influence on the translation of mRNAs.
Chan
Chia C
CC
Howard Hughes Medical Institute and Department of Biochemistry & Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Dostie
Josee
J
Diem
Michael D
MD
Feng
Wenqin
W
Mann
Matthias
M
Rappsilber
Juri
J
Dreyfuss
Gideon
G
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism*; D039601:Eukaryotic Initiation Factor-4A / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D005091:Exons / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C105242:ALYREF protein, human; D000911:Antibodies, Monoclonal; C491494:MAGOH protein, human; D046911:Macromolecular Substances; C122111:NXF1 protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011506:Proteins; C406243:RBM8A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D039601:Eukaryotic Initiation Factor-4A