Pathologic effects of RNase-L dysregulation in immunity and proliferative control.
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.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Heather J
HJ
Ezelle
Bret A
BA
Hassel
D000818:Animals; D048708:Cell Growth Processes / Q000276:immunology; D004722:Endoribonucleases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000276:immunology; D012313:RNA / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D012313:RNA; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease