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

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.

• Authors: Heather J Ezelle, Bret A Hassel
• Journal: Frontiers in bioscience (Scholar edition) (Front Biosci (Schol Ed)) Vol. 4 Issue 2 Pg. 767-86 (01 01 2012) ISSN: 1945-0524 [Electronic] Singapore
• PMID: 22202089 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)

Chemical References

• RNA
• Endoribonucleases
• 2-5A-dependent ribonuclease

Topics

• Animals
• Cell Growth Processes (immunology)
• Endoribonucleases (genetics, immunology, metabolism)
• Humans
• Neoplasms (enzymology, immunology)
• RNA (genetics, immunology, metabolism)