Source: J Biol Chem 2002 Jul 12; [epub ahead of print]
Demettre E, Bastide L, D’Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B.
UMR 5124, CNRS, Montpellier 34293.
A 37 kDa binding polypeptide accumulates in peripheral blood mononuclear cells (PBMC) extracts from Chronic Fatigue Syndrome (CFS) patients and is being considered as a potential diagnostic marker (1). 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 (HLE). RNase L proteolysis leads to the accumulation of two major fragments with molecular weights 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 kDa and 37 kDa fragments by proteases of CFS PBMC extract or by purified HLE. 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. (1)De Meirleir, K., Bisbal, C., Campine, I., De Becker, P., Salehzada, T., Demettre, E., and Lebleu, B. (2000) Am J Med 108(2), 99-105.
PMID: 12118002 [PubMed – as supplied by publisher]