Ribonuclease L

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Ribonuclease L or RNase L is a latent enzyme that cleaves the components of RNA. Its increased production is activated by interferon which, in turn, causes the destruction of all RNA within the cell, both cellular and viral. It is a key component of the intracellular immune response to viral pathogens.

RNase L is present in small quantities during the normal cell cycle. When interferon binds to receptors on the cell membrane, it triggers the production of more RNase L along with 2'-5' Oligodenylate Synthetase (OAS). OAS converts ATP to pyrophosphate and 2'-5'linked oligoadenylates. The 2-5 A molecules bind to RNase L and activates it. The activated RNaseL destroys all cellular and viral RNA, which triggers autophagy and programmed cell death.

Several abnormalities of the 2-5A/RNaseL pathways have been documented in chronic fatigue syndrome patients and have been suggested a possible diagnostic biomarker. Studies of peripheral blood mononuclear cells have found that the RNase L and 2-5 A pathways are upregulated.[1][dead link], with abnormally high levels of the active form of 2-5 A.[2] RNase L proteins of the molecular weights 80, 42 and 37 kDa have also been found.[3]

RNaseL activity and concentrations of bioactive 2-5 A are correlated with physical function.[4]

Notable studies[edit | edit source]

  • 2001, G-Actin Cleavage Parallels 2-5A-Dependent RNase L Cleavage in Peripheral Blood Mononuclear Cells—Relevance to a Possible Serum-Based Screening Test for Dysregulations in the 2-5A Pathway[5](Abstract)
  • 2001, Interactions Between Rnase L Ankyrin-Like Domain and ABC Transporters as a Possible Origin for Pain, Ion Transport, CNS and Immune Disorders of Chronic Fatigue Immune Dysfunction Syndrome[6](Abstract)

See also[edit | edit source]

References[edit | edit source]

  1. http://cid.oxfordjournals.org/content/18/Supplement_1/S96.short
  2. Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Müller WE, Schröder HC, Carter WA, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. PMID: 8148461
  3. Suhadolnik RJ, Peterson DL, O'Brien K, Cheney PR, Herst CV, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, et al. 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. doi:10.1089/jir.1997.17.377 PMID: 9243369
  4. 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
  5. Simon Roelens, C. Vincent Herst, Anne D'Haese, Karen De Smet, Marc Frémont, Kenny De Meirleir & Patrick Englebienne. (2001). G-Actin Cleavage Parallels 2-5A-Dependent RNase L Cleavage in Peripheral Blood Mononuclear Cells—Relevance to a Possible Serum-Based Screening Test for Dysregulations in the 2-5A Pathway. Journal of Chronic Fatigue Syndrome, Vol. 8, Iss. 3-4, pp. 63-82. http://dx.doi.org/10.1300/J092v08n03_07
  6. Patrick Englebienne, C. Vincent Herst, Karen De Smet, Anne D'Haese & Kenny De Meirleir. (2001). Interactions Between Rnase L Ankyrin-Like Domain and ABC Transporters as a Possible Origin for Pain, Ion Transport, CNS and Immune Disorders of Chronic Fatigue Immune Dysfunction Syndrome. Journal of Chronic Fatigue Syndrome, Vol. 8, Iss. 3-4, pp. 83-102. http://dx.doi.org/10.1300/J092v08n03_08

enzyme - a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.

cell membrane - A very thin membrane, composed of lipids and protein, that surrounds the cytoplasm of a cell and controls the passage of substances into and out of the cell.

apoptosis - a type of cell death in which a cell, in response to a threat, initiates a series of molecular steps that lead to its orderly death. This is one method the body uses to get rid of unneeded or abnormal cells. This form of cell suicide is also called programmed cell death.

serum - The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

chronic fatigue syndrome (CFS) - A controversial term, invented by the U.S. Centers for Disease Control, that generally refers to a collection of symptoms as “fatigue”. There have been multiple attempts to come up with a set of diagnostic criteria to define this term, but few of those diagnostic criteria are currently in use. Previous attempts to define this term include the Fukuda criteria and the Oxford criteria. Some view the term as a useful diagnostic category for people with long-term fatigue of unexplained origin. Others view the term as a derogatory term borne out of animus towards patients. Some view the term as a synonym of myalgic encephalomyelitis, while others view myalgic encephalomyelitis as a distinct disease.

myalgic encephalomyelitis (ME) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

chronic fatigue syndrome (CFS) - A controversial term, invented by the U.S. Centers for Disease Control, that generally refers to a collection of symptoms as “fatigue”. There have been multiple attempts to come up with a set of diagnostic criteria to define this term, but few of those diagnostic criteria are currently in use. Previous attempts to define this term include the Fukuda criteria and the Oxford criteria. Some view the term as a useful diagnostic category for people with long-term fatigue of unexplained origin. Others view the term as a derogatory term borne out of animus towards patients. Some view the term as a synonym of myalgic encephalomyelitis, while others view myalgic encephalomyelitis as a distinct disease.

Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) - Chronic Fatigue and Immune Dysfunction Syndrome is another term for Chronic Fatigue Syndrome, but one which emphasizes the immunological aspects of the disease. Popular in the 1990's, this term has apparently fallen into disuse.

The information provided at this site is not intended to diagnose or treat any illness.
From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history.