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

TY - JOUR

T1 - A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development

AU - Nielsen, J

AU - Christiansen, J

AU - Lykke-Andersen, J

AU - Johnsen, A H

AU - Wewer, Ulla M.

AU - Nielsen, F C

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - 3T3 Cells

KW - Amino Acid Sequence

KW - Animals

KW - Binding Sites

KW - Cell Line

KW - Chickens

KW - Cloning, Molecular

KW - DNA, Complementary

KW - Embryonic and Fetal Development

KW - Gene Expression Regulation, Developmental

KW - Humans

KW - Insulin-Like Growth Factor II

KW - Mice

KW - Molecular Sequence Data

KW - Protein Biosynthesis

KW - RNA, Messenger

KW - RNA-Binding Proteins

KW - Sequence Homology, Amino Acid

KW - Xenopus

M3 - Journal article

C2 - 9891060

SN - 0270-7306

VL - 19

SP - 1262

EP - 1270

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 2

ER -