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Basis for regulated RNA cleavage by functional analysis of RNase L and Ire1p

Published online by Cambridge University Press:  07 March 2001

BEIHUA DONG ,
MAHO NIWA ,
PETER WALTER  and
ROBERT H. SILVERMAN
BEIHUA DONG
Affiliation:
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
MAHO NIWA
Affiliation:
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco, California 94143, USA
PETER WALTER
Affiliation:
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco, California 94143, USA
ROBERT H. SILVERMAN
Affiliation:
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
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Abstract

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/threonine kinase and endoribonuclease. To probe their similarities and differences, molecular properties of wild-type and mutant forms of human RNase L and yeast Ire1p were compared. Surprisingly, RNase L and Ire1p showed mutually exclusive RNA substrate specificity and partially overlapping but not identical requirements for phylogenetically conserved amino acid residues in their nuclease domains. A functional model for RNase L was generated based on the comparative analysis with Ire1p that assigns novel roles for ankyrin repeats and kinase-like domains.

Keywords

interferonribonucleaseRNA stabilityunfolded protein response
Type
Research Article
Information
RNA , Volume 7 , Issue 3 , March 2001 , pp. 361 - 373
Copyright
© 2001 RNA Society

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