title: Induction of cap-independent BiP (hsp-3) and Bcl-2 (ced-9) translation in response to eIF4G (IFG-1) depletion in C. elegans.
abstract: During apoptosis, activated caspases cleave the translation initiation factor eIF4G. This cleavage disrupts cap-dependent mRNA translation initiation within the cell. However, a specific subset of mRNAs can still be recruited for protein synthesis in a cap-independent manner by the residual initiation machinery. Many of these mRNAs, including cell death related mRNAs, contain internal ribosome entry sites (IRESes) that promote their enhanced translation during apoptosis. Still other mRNAs have little dependence on the cap recognition mechanism. The expression of the encoded proteins, both anti- and pro-apoptotic, allows for an initial period of attempted cell survival, then commitment to cell death when damage is extensive. In this study we address the translational regulation of the stress and apoptosis-related mRNAs in C. elegans: BiP (hsp-3) (hsp-4), Hif-1 (hif-1), p53 (cep-1), Bcl-2 (ced-9) and Apaf-1 (ced-4). Altered translational efficiency of these messages was observed upon depletion of cap-dependent translation and induction of apoptosis within the C. elegans gonad. Our findings suggest a physiological link between the cap-independent mechanism and the enhanced translation of hsp-3 and ced-9. This increase in the efficiency of translation may be integral to the stress response during the induction of physiological apoptosis.
authors.affiliation: Department of Biochemistry and Molecular Biology; Brody School of Medicine at East Carolina University; Greenville, NC USA.
authors.forename: J Kaitlin
authors.initials: JK
authors.lastname: Morrison
authors.affiliation: Department of Biochemistry and Molecular Biology; Brody School of Medicine at East Carolina University; Greenville, NC USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Friday
authors.affiliation: Department of Biochemistry and Molecular Biology; Brody School of Medicine at East Carolina University; Greenville, NC USA; Department of Biochemistry and Molecular Biology; Debusk College of Osteopathic Medicine; Lincoln Memorial University; Harrogate, TN USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Henderson
authors.affiliation: Department of Biochemistry and Molecular Biology; Brody School of Medicine at East Carolina University; Greenville, NC USA.
authors.forename: Enhui
authors.initials: E
authors.lastname: Hao
authors.affiliation: Department of Biochemistry and Molecular Biology; Brody School of Medicine at East Carolina University; Greenville, NC USA.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Keiper
keywords: Apaf-1; Bcl-2; BiP; cap-independent translation; eIF4G; germ cell apoptosis