Regulation of cap-dependent translation initiation in the early stage porcine parthenotes.
The binding of mRNAs to ribosomes is mediated by the protein complex eIF4F in conjunction with eIF4B (eukaryotic initiation factor 4F and 4B). EIF4F is a three subunit complex consisting of eIF4A (RNA helicase), eIF4E (mRNA cap binding protein), and eIF4G (bridging protein). The crucial role is played by eIF4E, which directly binds the 5'-cap structure of the mRNA and facilitates the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. EIF4E binding to mRNA and to other initiation factors is regulated on several levels, including its phosphorylation on Ser-209, and association with its regulatory protein 4E-binding protein (4E-BP1). In this study we document that both the translation initiation factor eIF4E and its regulator 4E-BP1 become dephosphorylated in the early stage porcine zygotes already 8 hr post-activation. Similarly, the activities of ERK1/2 MAP and Mnk1 kinases, which are both involved in eIF4E phosphorylation, gradually decrease during this period with the timing similar to that of eIF4E dephosphorylation. The formation of an active eIF4F complex is also diminished after 9-15 hr post-activation, although substantial amounts of this complex have been detected also 24 hr post-activation (2-cell stage). The overall protein synthesis in the parthenotes decreases gradually from 12 hr post-activation reaching a minimum after 48 hr (4-cell stage). Although the translation is gradually decreasing during early preimplantation development, the eIF4F complex, which is temporarily formed, might be a premise for the translation of a small subset of mRNAs at this period of development.
Susor
Andrej
A
Institute of Animal Physiology and Genetics, Libechov, Czech Republic.
Jelínková
Lucie
L
Karabínová
Pavla
P
Torner
Helmut
H
Tomek
Wolfgang
W
Kovárová
Hana
H
Kubelka
Michal
M
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D005260:Female; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010312:Parthenogenesis / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D012315:RNA Caps / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D015053:Zygote / Q000166:cytology / Q000378:metabolism*
D002352:Carrier Proteins; D039562:Eukaryotic Initiation Factor-4F; D039642:Eukaryotic Initiation Factors; D012315:RNA Caps; C031799:eIF-4B; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3