Depletion of the cap-associated isoform of translation factor eIF4G induces germline apoptosis in C. elegans.
During mammalian programmed cell death, cleavage of the translation initiation factor 4G proteins (eIF4GI and eIF4GII) by caspase-3 induces the cap-independent synthesis of pro-apoptotic proteins. Apoptosis occurs naturally in the gonad to remove germ cells that are not selected to grow as oocytes and mature into eggs. Here, we describe two major isoforms of Caenorhabditis elegans eIF4G that are derived from a single gene (ifg-1) and their separate roles in germline homeostasis. Full length IFG-1 protein (170 kDa isoform) differs from the shorter isoform (130 kDa) by the inclusion of the N-terminal domain containing the putative eIF4E-binding site required for mRNA cap recognition. Depletion of the cap-associated p170 isoform induced CED-4 expression in oocytes and markedly increased germline apoptotic events, but did not prevent early mitotic germ cell proliferation. Loss of both p170 and p130 suppressed germ cell proliferation and arrested larval development. Evidence suggests that eIF4G isoforms are differentially utilized during oogenesis to regulate germ cell apoptosis. We propose that an alternative mechanism to eIF4G cleavage may be employed in germ cells by changing the availability of the p170 isoform.
Contreras
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Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Richardson
M A
MA
Hao
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E
Keiper
B D
BD
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism*; D005718:Gametogenesis; D005854:Germ Cells / Q000166:cytology*; D006706:Homeostasis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism*; D012315:RNA Caps / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; D039603:Eukaryotic Initiation Factor-4G; D020033:Protein Isoforms; D012315:RNA Caps; D012333:RNA, Messenger