Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities

Pizzo, Elio; Sarcinelli, Carmen; Sheng, Jinghao; Fusco, Sabato; Formiggini, Fabio; Netti, Paolo A.; Yu, Wenhao; D’Alessio, Giuseppe; Hu, Guo‐fu

doi:10.1242/jcs.134551

Cited by 102 publications

(122 citation statements)

References 55 publications

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“…S7B). These results suggest that SHOT-RNA generation may not be regulated by RNH1, in contrast to the case of tiRNAs, where the quantitative changes in RNH1 regulate expression (29).…”

Section: Abundant Accumulation Of Trna Halves In Specific Breast Andmentioning

confidence: 77%

Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

Honda

Loher

Shigematsu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

310

464

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Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOTRNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER − breast cancer, AR − prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5′-and 3′-SHOT-RNAs, corresponding to 5′-and 3′-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3′-end, respectively. By devising a "cP-RNA-seq" method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5′-SHOT-RNAs. Furthermore, 5′-SHOT-RNA, but not 3′-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets.tRNA | tRNA half | sex hormone | breast cancer | prostate cancer

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“…S7B). These results suggest that SHOT-RNA generation may not be regulated by RNH1, in contrast to the case of tiRNAs, where the quantitative changes in RNH1 regulate expression (29).…”

Section: Abundant Accumulation Of Trna Halves In Specific Breast Andmentioning

confidence: 77%

Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

Honda

Loher

Shigematsu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

310

464

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“…The mechanism by which ER stress promotes ANG-RNH1 dissociation is not known, but might involve RNH1 nuclear translocation. 29 In parallel, during ER stress ANG mRNA expression increases under the control of the IRE1a-XBP1 axis, as well as protein level, albeit to a lesser extent, maybe because the protein is in part secreted. Newly produced ANG is also involved in cytoprotection, and we cannot exclude that ANG has cytoprotective properties independent of tiRNA production.…”

Section: Discussionmentioning

confidence: 98%

“…We first analyzed the interaction of ANG and the ribonuclease inhibitor ribonuclease/angiogenin inhibitor 1 (RNH1), an important regulator of ANG activity, whose dissociation under stress is required to allow ANG cellular activity. 29 Co-immunoprecipitation analysis revealed that the association of ANG and RNH1 was disrupted following 2 hours of exposure to tunicamycin ( Figure 4A), thus indicating that ER stress promotes the release of ANG from its inhibitor. Recent findings also indicate that during stress, ANG participates in the production of stress granules (SG).…”

Section: Ang Participates In Translation Inhibition During Er Stressmentioning

confidence: 99%

Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury

Mami

Bouvier

Karoui

et al. 2016

Journal of the American Society of Nephrology

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Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang 2/2 ) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stressmediated adaptive translational control mechanism.

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“…Cellular ANG is bound to RNH1, which prevents random cleavage of cellular RNA. It has also been reported that RNH1 regulates the subcellular localization of ANG to control growth and survival [50]. To date, a total of 19 unique ANG-interacting proteins have been reported with experimental evidence ( Table 2).…”

Section: Ang-interacting Proteinsmentioning

confidence: 98%

Three decades of research on angiogenin: a review and perspective

Sheng¹,

Xu²

2016

ABBS

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179

201

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As a member of the vertebrate-specific secreted ribonucleases, angiogenin (ANG) was first isolated and identified solely by its ability to induce new blood vessel formation, and now, it has been recognized to play important roles in various physiological and pathological processes through regulating cell proliferation, survival, migration, invasion, and/or differentiation. ANG exhibits very weak ribonucleolytic activity that is critical for its biological functions, and exerts its functions through activating different signaling transduction pathways in different target cells. A series of recent studies have indicated that ANG contributes to cellular nucleic acid metabolism. Here, we comprehensively review the results of studies regarding the structure, mechanism, and function of ANG over the past three decades. Moreover, current problems and future research directions of ANG are discussed. The understanding of the function and mechanism of ANG in a wide context will help to better delineate its roles in diseases, especially in cancer and neurodegenerative diseases.

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Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities

Cited by 102 publications

References 55 publications

Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury

Three decades of research on angiogenin: a review and perspective

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