Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients

J Biol Chem. 2002 Sep 20;277(38):35746-51. doi: 10.1074/jbc.M201263200. Epub 2002 Jul 12.

Abstract

A 37-kDa binding polypeptide accumulates in peripheral blood mononuclear cell (PBMC) extracts from chronic fatigue syndrome (CFS) patients and is being considered as a potential diagnostic marker (De Meirleir, K., Bisbal, C., Campine, I., De Becker, P., Salehzada, T., Demettre, E., and Lebleu, B. (2000) Am. J. Med. 108, 99-105). We establish here that this low molecular weight 2-5A-binding polypeptide is a truncated form of the native 2-5A-dependent ribonuclease L (RNase L), generated by an increased proteolytic activity in CFS PBMC extracts. RNase L proteolysis in CFS PBMC extracts can be mimicked in a model system in which recombinant RNase L is treated with human leukocyte elastase. RNase L proteolysis leads to the accumulation of two major fragments with molecular masses of 37 and 30 kDa. The 37-kDa fragment includes the 2-5A binding site and the N-terminal end of native RNase L. The 30-kDa fragment includes the catalytic site in the C-terminal part of RNase L. Interestingly, RNase L remains active and 2-5A-dependent when degraded into its 30- and 37-kDa fragments by proteases of CFS PBMC extract or by purified human leukocyte elastase. The 2-5A-dependent nuclease activity of the truncated RNase L could result from the association of these digestion products, as suggested in pull down experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Fatigue Syndrome, Chronic / blood
  • Fatigue Syndrome, Chronic / enzymology*
  • Humans
  • Hydrolysis
  • Monocytes / enzymology*
  • Recombinant Proteins / blood
  • Ribonucleases / blood*

Substances

  • Recombinant Proteins
  • 2',5'-Oligoadenylate Synthetase
  • Ribonucleases