SARS-Cov-2 In der Zuschrift aus S. 21830 berichten Xinjing Tang et al. über die effiziente Hemmung von SARS-CoV-2 mit chimären Antisense-Oligonukleotiden durch Aktivierung RNase L.

The RNASEL gene, a strong candidate for the hereditary prostate cancer 1 allele (HPC1), encodes a single-stranded specific endoribonuclease involved in the antiviral actions of IFNs. RNase L is activated enzymatically after binding to unusual 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A). Biostable phosphorothioate analogues of 2-5A were synthesized chemically and used to study the eff...

The hereditary prostate cancer 1 (HPC1) allele maps to the RNASEL gene encoding a protein (RNase L) implicated in the antiviral activity of interferons. To investigate the possible role of RNase L in apoptosis of prostate cancer cells, we decreased levels of RNase L by severalfold in the DU145 human prostate cancer cell line through the stable expression of a small interfering RNA (siRNA). Cont...

The endoribonuclease RNase-L is the terminal component of an RNA cleavage pathway that mediates antiviral, antiproliferative and immunomodulatory activities. Inactivation or dysregulation of RNase-L is associated with a compromised immune response and increased risk of cancer, accordingly its activity is tightly controlled and requires an allosteric activator, 2',5'-linked oligoadenylates, for ...

The deregulation of the 2.5A synthetase RNase L antiviral pathway and the prevalence of Mycoplasma spp. in subsets of Chronic Fatigue Syndrome [CFS] have been separately reported in the scientific literature. We hypothesised that a co-morbid pathophysiological mechanism involving infection by Mycoplasma spp. and the deregulation of the 2,5A synthetase / RNase L antiviral pathway may exist in CF...

We report our studies to probe the possible role of the host response to double-stranded RNA in cessation of alphavirus minus-strand synthesis. Mouse embryo fibroblasts (MEF) from Mx1-deficient mice that also lack either the protein kinase R (PKR) or the latent RNase L or both PKR and RNase L were screened. In RNase L-deficient but not wild-type or PKR-deficient MEF, there was continuous synthe...

Chronic fatigue syndrome (CFS) is a disorder characterized by debilitating fatigue associated with immunological abnormalities. The etiology remains unclear. A low-molecular-mass (37 kDa) isoform of RNase L has been described in peripheral blood mononuclear cell (PBMC) extracts, and the ratio of two isoforms of RNase L (37 kDa/83 kDa) has been proposed as a potential biochemical marker of CFS. ...

RNase L and Ire1p are members of a superfamily of regulated endoribonucleases that play essential roles in mediating diverse types of cellular stress responses. 2'-5' oligoadenylates, produced in response to interferon treatment and viral double-stranded RNA, are necessary to activate RNase L. In contrast, unfolded proteins in the endoplasmic reticulum activate Ire1p, a transmembrane serine/thr...

2',5'-Oligoadenylate-dependent RNase L functions in the interferon-inducible, RNA decay pathway known as the 2-5A system. To determine the physiological roles of the 2-5A system, mice were generated with a targeted disruption of the RNase L gene. The antiviral effect of interferon alpha was impaired in RNase L-/- mice providing the first evidence that the 2-5A system functions as an antiviral p...

The p21(Cip1/WAF1) plays an important role in cell-cycle arrest. Here, we find that RNase L regulates p21-mediated G(1) growth arrest in AU-rich elements-dependent manner. We found a significant loss of p21 mRNA expression in RNASEL(-/-) MEFs and that the overexpression of RNase L in HeLa cells induces p21 mRNA expression. The p21 mRNA half-life significantly changes as a result of RNase L modu...