Deletion of the 3'-untranslated region of aspartylglucosaminidase mRNA results in a lysosomal accumulation disease

J Biol Chem. 1992 May 5;267(13):8715-8.

Abstract

Aspartylglucosaminuria (AGU) is a lysosomal storage disease due to mutations in the aspartylglucosaminidase (AGA) gene. The deficient enzyme activity in patients' cells blocks one of the final steps in the degradation of N-linked glycoproteins. All the AGU mutations identified so far affect the coding region of the AGA gene. Here we report a homozygous 876-base pair deletion, which removes the 3'-noncoding area but leaves the coding region of the AGA mRNA intact. This deletion does not prevent transcription termination or polyadenylation of the patient's truncated mRNA, and the steady state level of the mRNA is comparable with the control. However, the quantity of AGA polypeptide chains in the patient's fibroblasts is negligible. This suggests that the deletion interferes with the translational efficiency in vivo and provides a unique model to pursue the biological significance of untranslated regions of human mRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartylglucosylaminase / genetics*
  • Base Sequence
  • Blotting, Southern
  • Blotting, Western
  • Cells, Cultured
  • Chromosome Deletion*
  • DNA / genetics
  • Homozygote
  • Humans
  • Introns
  • Lysosomal Storage Diseases / genetics*
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • RNA, Messenger / genetics*
  • Transcription, Genetic

Substances

  • RNA, Messenger
  • DNA
  • Aspartylglucosylaminase