Human angiogenin is a potent cytotoxin in the absence of ribonuclease inhibitor.

Thomas, Sydney P; Hoang, Trish T; Ressler, Valerie T; Raines, Ronald T

Thomas, Sydney P; Hoang, Trish T; Ressler, Valerie T; Raines, Ronald T.

Afiliación

Thomas SP; Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Hoang TT; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Ressler VT; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Raines RT; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

RNA ; 24(8): 1018-1027, 2018 08.

Article en En | MEDLINE | ID: mdl-29748193

RESUMEN

Angiogenin (ANG) is a secretory ribonuclease that promotes the proliferation of endothelial cells, leading to angiogenesis. This function relies on its ribonucleolytic activity, which is low for simple RNA substrates. Upon entry into the cytosol, ANG is sequestered by the ribonuclease inhibitor protein (RNH1). We find that ANG is a potent cytotoxin for RNH1-knockout HeLa cells, belying its inefficiency as a nonspecific catalyst. The toxicity does, however, rely on the ribonucleolytic activity of ANG and a cytosolic localization, which lead to the accumulation of particular tRNA fragments (tRFs), such as tRF-5 Gly-GCC. These up-regulated tRFs are highly cytotoxic at physiological concentrations. Although ANG is well-known for its promotion of cell growth, our results reveal that ANG can also cause cell death.

Asunto(s)

Proteínas Portadoras/metabolismo; Muerte Celular/fisiología; Citotoxinas/metabolismo; ARN de Transferencia/genética; Ribonucleasa Pancreática/metabolismo; Sistemas CRISPR-Cas; Proteínas Portadoras/genética; Muerte Celular/genética; Línea Celular Tumoral; Proliferación Celular; Citotoxinas/genética; Técnicas de Inactivación de Genes; Células HeLa; Humanos; MicroARNs/genética; Estrés Oxidativo; Unión Proteica/genética; Ribonucleasa Pancreática/genética

Palabras clave

CRISPR; RNA processing; oxidative stress ribonuclease inhibitor; tRNA-derived fragment

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleasa Pancreática / ARN de Transferencia / Proteínas Portadoras / Muerte Celular / Citotoxinas Límite: Humans Idioma: En Revista: RNA Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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