The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins

RNA. 1997 Dec;3(12):1421-33.

Abstract

Translation of hunchback(mat) (hb[mat]) mRNA must be repressed in the posterior of the pre-blastoderm Drosophila embryo to permit formation of abdominal segments. This translational repression requires two copies of the Nanos Response Element (NRE), a 16-nt sequence in the hb[mat] 3' untranslated region. Translational repression also requires the action of two proteins: Pumilio (PUM), a sequence-specific RNA-binding protein; and Nanos, a protein that determines the location of repression. Binding of PUM to the NRE is thought to target hb(mat) mRNA for repression. Here, we show the RNA-binding domain of PUM to be an evolutionarily conserved, 334-amino acid region at the carboxy-terminus of the approximately 158-kDa PUM protein. This contiguous region of PUM retains the RNA-binding specificity of full-length PUM protein. Proteins with sequences homologous to the PUM RNA-binding domain are found in animals, plants, and fungi. The high degree of sequence conservation of the PUM RNA-binding domain in other far-flung species suggests that the domain is an ancient protein motif, and we show that conservation of sequence reflects conservation of function: that is, the homologous region from a human protein binds RNA with sequence specificity related to but distinct from Drosophila PUM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence / genetics*
  • DNA-Binding Proteins / genetics
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics
  • Humans
  • Insect Proteins / genetics*
  • Molecular Sequence Data
  • Mutation
  • Protein Biosynthesis / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Insect Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Transcription Factors
  • hb protein, Drosophila
  • pum protein, Drosophila