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

Mol Cell Biol. 1999 Feb;19(2):1262-70. doi: 10.1128/MCB.19.2.1262.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • DNA, Complementary
  • RNA, Messenger
  • RNA-Binding Proteins
  • Insulin-Like Growth Factor II

Associated data

  • GENBANK/AF117106
  • GENBANK/AF117107
  • GENBANK/AF117108