The gene for histone RNA hairpin binding protein is located on human chromosome 4 and encodes a novel type of RNA binding protein

F Martin, A Schaller, S Eglite, D Schümperli, Berndt Marino Muller

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136 Citations (Scopus)


The hairpin structure at the 3' end of animal histone mRNAs controls histone RNA 3' processing, nucleocytoplasmic transport, translation and stability of histone mRNA. Functionally overlapping, if not identical, proteins binding to the histone RNA hairpin have been identified in nuclear and polysomal extracts. Our own results indicated that these hairpin binding proteins (HBPs) bind their target RNA as monomers and that the resulting ribonucleoprotein complexes are extremely stable. These features prompted us to select for HBP-encoding human cDNAs by RNA-mediated three-hybrid selection in Saccharomyces cerevesiae. Whole cell extract from one selected clone contained a Gal4 fusion protein that interacted with histone hairpin RNA in a sequence- and structure-specific manner similar to a fraction enriched for bovine HBP, indicating that the cDNA encoded HBP. DNA sequence analysis revealed that the coding sequence did not contain any known RNA binding motifs. The HBP gene is composed of eight exons covering 19.5 kb on the short arm of chromosome 4. Translation of the HBP open reading frame in vitro produced a 43 kDa protein with RNA binding specificity identical to murine or bovine HBP. In addition, recombinant HBP expressed in S. cerevisiae was functional in histone pre-mRNA processing, confirming that we have indeed identified the human HBP gene.
Original languageEnglish
Pages (from-to)769-778
Number of pages10
JournalEMBO Journal
Issue number4
Publication statusPublished - 17 Feb 1997


  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cattle
  • Chromosome Mapping
  • Chromosomes, Human, Pair 4
  • Cloning, Molecular
  • DNA, Complementary
  • Exons
  • Gene Expression
  • Genes
  • Genetic Complementation Test
  • Histones
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins
  • Nucleic Acid Conformation
  • Organ Specificity
  • Promoter Regions, Genetic
  • RNA
  • RNA Precursors
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae
  • Sequence Analysis, DNA
  • mRNA Cleavage and Polyadenylation Factors
  • histone gene expression
  • pre-mRNA processing
  • RNA 3' processing
  • RNA–protein interaction
  • yeast three-hybrid system


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