title: DAP5 associates with eIF2β and eIF4AI to promote Internal Ribosome Entry Site driven translation.
abstract: Initiation is a highly regulated rate-limiting step of mRNA translation. During cap-dependent translation, the cap-binding protein eIF4E recruits the mRNA to the ribosome. Specific elements in the 5'UTR of some mRNAs referred to as Internal Ribosome Entry Sites (IRESes) allow direct association of the mRNA with the ribosome without the requirement for eIF4E. Cap-independent initiation permits translation of a subset of cellular and viral mRNAs under conditions wherein cap-dependent translation is inhibited, such as stress, mitosis and viral infection. DAP5 is an eIF4G homolog that has been proposed to regulate both cap-dependent and cap-independent translation. Herein, we demonstrate that DAP5 associates with eIF2β and eIF4AI to stimulate IRES-dependent translation of cellular mRNAs. In contrast, DAP5 is dispensable for cap-dependent translation. These findings provide the first mechanistic insights into the function of DAP5 as a selective regulator of cap-independent translation.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 7610001, Israel nliberman@genetics.med.harvard.edu.
authors.forename: Noa
authors.initials: N
authors.lastname: Liberman
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada Rosalind and Morris Goodman Cancer Centre, Montréal, Québec H3A 1A3, Canada valentina.gandin@mail.mcgill.ca.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada Rosalind and Morris Goodman Cancer Centre, Montréal, Québec H3A 1A3, Canada.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Svitkin
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: David
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada Groupe de Recherche Axé sur la Structure des Protéines, Montréal, Québec H3A 1A3, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Virgili
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada Rosalind and Morris Goodman Cancer Centre, Montréal, Québec H3A 1A3, Canada.
authors.forename: Maritza
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Holcik
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada Groupe de Recherche Axé sur la Structure des Protéines, Montréal, Québec H3A 1A3, Canada.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Nagar
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Kimchi
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada Rosalind and Morris Goodman Cancer Centre, Montréal, Québec H3A 1A3, Canada nahum.sonenberg@mcgill.ca.
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D010448:Peptide Initiation Factors / Q000378:metabolism*; D014176:Protein Biosynthesis; D012315:RNA Caps; D012270:Ribosomes / Q000378:metabolism*
chemical_list: C491300:EIF4G2 protein, human; D020717:Eukaryotic Initiation Factor-2B; D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; D012315:RNA Caps; C075833:eIF-4