ME and CFS Medical Abnormalities – Rnase-L Issues


Following is a list of articles about abnormalities with Rnase-L in ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the ME and CFS Medical Abnormalities page of this website.


Nijs J, Frémont M. Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications. Expert Opin Ther Targets. 2008 Mar;12(3):281-9. PMID: 18269338

Proteolytic cleavage of the native RNase L enzyme is characteristic of the dysregulation of intracellular immunity in CFS.


Bisbal C, Silverman RH. Diverse functions of RNase L and implications in pathology. Biochimie. 2007 Jun-Jul;89(6-7):789-98.  PMID: 17400356

The role of RNase-L, known to be dysfunctional in CFS, is discussed.


Nijs J, De Meirleir K. Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome. In Vivo. 2005 Nov-Dec;19(6):1013-21. PMID: 16277015

The 2-5A synthetase/RNase L pathway in CFS patients appears to be both up-regulated (i.e. increased levels of bioactive 2-5A synthetase and increased activity of the RNase L enzyme) and deregulated (elastase and calpain initiate 83 kDa RNase L proteolysis, generating two major fragments with molecular masses of 37 and 30 kDa, respectively). The deregulation of the 2-5A synthetase/RNase L pathway in CFS accompanies decreased NK-function and deregulation of apoptotic pathways. Various components of the pathway appear to be related to performance during a graded exercise stress test.


Frémont M, El Bakkouri K, Vaeyens F, Herst CV, De Meirleir K, Englebienne P. 2′,5′-Oligoadenylate size is critical to protect RNase L against proteolytic cleavage in chronic fatigue syndrome. Exp Mol Pathol. 2005 Jun;78(3):239-46. PMID: 15924878

CFS patients have disruptions in immune activity in the form of a dysregulation in the 2′,5′-oligoadenylate (2-5A)-dependent RNase L antiviral pathway in peripheral blood mononuclear cells (PBMC) of CFS.  This is characterized by upregulated 2-5A synthetase and RNase L activities, as well as by the presence of a low molecular weight (LMW) 2-5A-binding protein of 37-kDa related to RNase L.


Tiev KP, Demettre E, Ercolano P, Bastide L, Lebleu B, Cabane J. RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome. Clin Diagn Lab Immunol. 2003 Mar;10(2):315-6. PMID: 12626460

In the absence of acute infection or chronic inflammation, a high RNase L ratio could distinguish CFS patients from healthy volunteers.


Demettre E, Bastide L, D’Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B. Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem. 2002 Sep 20;277(38):35746-51. PMID: 12118002

A 37-kDa binding polypeptide accumulates in peripheral blood mononuclear cell (PBMC) extracts from CFS patients and is being considered as a potential diagnostic marker. The authors 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.


Snell CR, Vanness JM, Strayer DR, Stevens SR. Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome. In Vivo. 2002 Mar-Apr;16(2):107-9. PMID:12073768

Amongst a group of CFS patients, a group with elevated Rnase L had a lower peak V02 and duration than the normal group, but a higher performance score. The results suggest that both exercise testing and the RNase L biomarker have potential to aid in the diagnosis of CFS.


Shetzline SE, Martinand-Mari C, Reichenbach NL, Buletic Z, Lebleu B, Pfleiderer W, Charubala R, De Meirleir K, De Becker P, Peterson DL, Herst CV, Englebienne P, Suhadolnik RJ. Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res. 2002 Apr;22(4):443-56. PMID: 12034027

A 2′,5′-oligoadenylate (2-5A)-dependent 37-kDa form of RNase L has been reported in extracts of peripheral blood mononuclear cells (PBMC) from individuals with chronic fatigue syndrome (CFS). The authors examined the biochemical relationship between the 80-kDa RNase L in healthy control PBMC and the 37-kDa RNase L in PBMC from individuals with CFS.


Vojdani A, Choppa PC, Lapp CW. Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome. J Clin Lab Immunol. 1998;50(1):1-16. PMID: 10189612

We investigated the levels of 2-5A synthetase, RNase L and RLI in patients with CFIDS and found a statistically significant decrease in RLI mRNA. The increased activation of RNase L may result in an increased cellular RNA turnover and subsequent inhibition of protein synthesis; thus resulting in general fatigue, myalgia muscle weakness and other symptomatologies shown in CFIDS patients.


Suhadolnik RJ, Peterson DL, O’Brien K, Cheney PR, Herst CV, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K, De Becker P, Charubala R, Pfleiderer W. Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res. 1997 Jul;17(7):377-85. PMID: 9243369

The authors present evidence suggesting that the RNase L enzyme dysfunction in CFS is more complex than previously reported.


Suhadolnik RJ, Reichenbach NL, Hitzges PM, Ablashi DV, Strayer DR, Carter WA. RNA drug therapy acting via the 2-5A synthetase/RNase L pathway. Ann N Y Acad Sci. 1993 Jun 23;685:756-7. PMID: 8363281


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