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A family of insulin-like growth factor I ... translation in late development


A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development.

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Insulin-like growth factor II (IGF-II) is a major fetal growth factor. The IGF-II gene generates multiple mRNAs with different 5' untranslated regions (5' UTRs) that are translated in a differential manner during development. We have identified a human family of three IGF-II mRNA-binding proteins (IMPs) that exhibit multiple attachments to the 5' UTR from the translationally regulated IGF-II leader 3 mRNA but are unable to bind to the 5' UTR from the constitutively translated IGF-II leader 4 mRNA. IMPs contain the unique combination of two RNA recognition motifs and four hnRNP K homology domains and are homologous to the Xenopus Vera and chicken zipcode-binding proteins. IMP localizes to subcytoplasmic domains in a growth-dependent and cell-specific manner and causes a dose-dependent translational repression of IGF-II leader 3 -luciferase mRNA. Mouse IMPs are produced in a burst at embryonic day 12.5 followed by a decline towards birth, and, similar to IGF-II, IMPs are especially expressed in developing epithelia, muscle, and placenta in both mouse and human embryos. The results imply that cytoplasmic 5' UTR-binding proteins control IGF-II biosynthesis during late mammalian development.


Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC

Molecular and cellular biology

1999-02-01 00:00

19

2

1262-70

3T3 Cells,Amino Acid Sequence,Animals,Binding Sites,Cell Line,Chickens,Cloning, Molecular,DNA, Complementary,Embryonic and Fetal Development,Gene Expression Regulation, Developmental,Humans,Insulin-Like Growth Factor II,Mice,Molecular Sequence Data,Protein Biosynthesis,RNA, Messenger,RNA-Binding Proteins,Sequence Homology, Amino Acid,Xenopus,DNA, Complementary,RNA, Messenger,RNA-Binding Proteins,Insulin-Like Growth Factor II

RNA Regulation Centre, Institute of Molecular Biology, University of Copenhagen, Copenhagen, Denmark

Mol. Cell. Biol.


0270-7306




800

True

9891060

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