IMR Press / FBS / Volume 4 / Issue 2 / DOI: 10.2741/S298

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Pathologic effects of RNase-L dysregulation in immunity and proliferative control

Show Less
1 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2 Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore MD
3 Research Services, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201 USA

*Author to whom correspondence should be addressed.

Academic Editors: Kotb Abdelmohsen, Songbi Chen

Front. Biosci. (Schol Ed) 2012, 4(2), 767–786; https://doi.org/10.2741/S298
Published: 1 January 2012
(This article belongs to the Special Issue RNA binding proteins in disease)
Abstract

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 enzymatic activity. The biological activities of RNase-L are a result of direct and indirect effects of RNA cleavage and microarray analyses have revealed that RNase-L impacts the gene expression program at multiple levels. The identification of RNase-L-regulated RNAs has provided insights into potential mechanisms by which it exerts antiproliferative, proapoptotic, senescence-inducing and innate immune activities. RNase-L protein interactors have been identified that serve regulatory functions and are implicated as alternate mechanisms of its biologic functions. Thus, while the molecular details are understood for only a subset of RNase-L activities, its regulation by small molecules and critical roles in host defense and as a candidate tumor suppressor make it a promising therapeutic target.

Share
Back to top