Translational regulation of mitochondrial differentiation in neonatal rat liver. Specific increase in the translational efficiency of the nuclear-encoded mitochondrial beta-F1-ATPase mRNA.
Postnatal (1-h) mitochondrial differentiation in normal neonatal rat liver is regulated at the translational level (Izquierdo, J. M., Luis, A. M., and Cuezva, J. M. (1990) J. Biol. Chem. 265, 9090-9097). The rapid postnatal increase in liver global rate of protein synthesis preferentially affects mitochondrial proteins (Valcarce, C., Navarrete, R. M., Encabo, P., Loeches, E., Satrústegui, J., and Cuezva, J. M. (1988) J. Biol. Chem. 263, 7767-7775). Analysis of polysome profiles and determination of both eukaryotic initiation factor 2 (eIF-2) activity and amount of eIF-2 beta protein in the liver of fetal and 1-h-old neonatal rats, indicate a rapid activation of translation initiation without changes in the amount of the translational machinery available between both stages of liver development. Appearance of a more acidic eIF-2 beta-subunit form in two-dimensional Western blots from 1-h-old rat livers suggests that covalently regulated modifications of the initiation factor phosphoproteins might be responsible for increased translation in the neonatal liver. On the other hand, preferential cytosolic translation of the mitochondrial nuclear-encoded beta-F1-ATPase mRNA at this stage of liver development is accomplished by (i) the antenatal accumulation of this mRNA in the fetal liver in 5-6-fold excess than that found in adults, although fetal liver beta-F1-ATPase mRNA shows negligible translational efficiency when compared to the adult counterpart; (ii) a 2-fold increase of the stored beta-F1-ATPase mRNA being rapidly mobilized into cytosolic polyribosomes, and (iii) a 3-fold increase in the in vitro determined translational efficiency of beta-F1-ATPase mRNA. Increased translational efficiency of beta-F1-ATPase mRNA at 1-h postnatal is specific for the nuclear-encoded template since beta-tubulin mRNA did not show any postnatal alteration in its translational efficiency. The results presented suggest that developmental changes in the poly(A)+ RNA fraction or in the reporter template itself are responsible for the increased and preferential translation of the nuclear-encoded mitochondrial mRNAs needed for mitochondrial differentiation and, thus, for mammalian adaptation to the extrauterine environment.
Luis
A M
AM
Departamento de Biología Molecular, Universidad Autónoma de Madrid, Spain.
Izquierdo
J M
JM
Ostronoff
L K
LK
Salinas
M
M
Santarén
J F
JF
Cuezva
J M
JM
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology*; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D006180:Proton-Translocating ATPases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014404:Tubulin / Q000235:genetics
D015852:Eukaryotic Initiation Factor-2; D012333:RNA, Messenger; D014404:Tubulin; D006180:Proton-Translocating ATPases