Interaction of hnRNP A2/B1 isoforms with telomeric ssDNA and the in vitro function

Biochem Biophys Res Commun. 2001 Jan 26;280(3):625-30. doi: 10.1006/bbrc.2000.4173.

Abstract

Overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, especially of B1 has been reported as a useful marker to detect cancers in early stage, although the biological reason is not clear. A2/B1 proteins were previously reported to bind telomeric DNA repeats. Alternative splicing of A2/B1 gene produces abundant A2, less abundant B1, and testis-specific minor isoforms B0a and B0b. In this study, B1 and B0b that have the N-terminal 12 amino acid insertion were suggested to have higher affinities to telomeric single-stranded DNA (ssDNA) than A2 and B0a. Kinetic analyses using purified B1 and B0b indicated that they interact dynamically with a single array of telomeric repeats. Furthermore, functional assays demonstrated that B1 and B0b bind with telomeric repeats in a tandem fashion and protect them from a nuclease and promote telomerase activity. A2/B1 proteins, especially B1 and B0b, may function as telomeric ssDNA-binding proteins in cancer and reproductive cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Base Sequence
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism*
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B*
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Male
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Surface Plasmon Resonance
  • Telomerase / metabolism
  • Telomere / genetics
  • Telomere / metabolism*

Substances

  • DNA, Single-Stranded
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Protein Isoforms
  • Ribonucleoproteins
  • hnRNP A2
  • Telomerase