Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C

Selitsky, Sara R.; Baran-Gale, Jeanette; Honda, Masao; Yamane, Daisuke; Masaki, Takahiro; Fannin, Emily E.; Guerra, Bernadette; Shirasaki, Takayoshi; Shimakami, Tetsuro; Lanford, Robert E.; Lemon, Stanley M.; Sethupathy, Praveen

doi:10.1038/srep07675

Cited by 131 publications

(142 citation statements)

References 37 publications

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“…Following our report on the function of tRF5-GluCTC in regulating RSV replication [10,[22][23][24], many recent studies suggest the role of tRFs in infectious diseases; however, other important tRFs in infectious diseases have not been identified. Here, we identified two novel tRF(s), other than tRF5-GluCTC, that play a critical role in regulating RSV replication and the associated host responses.…”

Section: Discussionmentioning

confidence: 99%

Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection

Zhou

Liu

Chen

et al. 2017

Journal of General Virology

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in children from infancy up to early childhood. Recently, we demonstrated that RSV infection alters cellular small non-coding RNA (sncRNA) expression, most notably the tRNA-derived RNA fragments (tRFs). However, the functions of the tRFs in virus-host interaction are largely unknown. Herein, we examined the role of three RSV-induced tRFs derived from the 5-end of mature tRNAs decoding GlyCCC, LysCTT and CysGCA (named tRF5-GlyCCC, tRF5-LysCTT and tRF5-CysGCA, respectively) in controlling RSV replication. We found that tRF5-GlyCCC and tRF5-LysCTT, but not tRF5-CysGCA, promote RSV replication, demonstrating the functional specificity of tRFs. The associated molecular mechanisms underlying the functions of tRF5-GlyCCC and tRF5-LysCTT were also investigated. Regulating the expression and/or activity of these tRFs may provide new insights into preventive and therapeutic strategies for RSV infection. The study also accumulated data for future development of a tRF targeting algorithm.

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Section: Discussionmentioning

confidence: 99%

Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection

Zhou

Liu

Chen

et al. 2017

Journal of General Virology

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“…As one of the two RNases produced by primary T cells, ANG can suppress the replication of the X4 HIV strains [116]. ANG-mediated tiRNAs are also increased and abundant in chronic hepatitis B and C infection, suggesting that ANG may play roles in viral infection [117]. Moreover, ANG may have antiinflammatory activity because its protein concentrations in serum are increased during the inflammatory response or tumour necrosis factor alpha and interleukin -1β treatment [102,118,119].…”

Section: Ang Participates In Immune Responsesmentioning

confidence: 99%

Three decades of research on angiogenin: a review and perspective

Sheng¹,

Xu²

2016

ABBS

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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“…In cytoplasm, ANG acts as a RNase cleaving tRNA and producing tRNA-halves, which has been reported to be reduced in liver cancer [47]. In nucleus, ANG is involved in up-regulating rRNA expression [36] or promoting angiogenesis [48], which then stimulates tumor cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

HBV Facilitated Hepatocellular Carcinoma Cells Proliferation by Up-Regulating Angiogenin Expression Through IL-6

Zhou

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Patients with hepatitis B virus (HBV) infection are at a high risk of developing hepatocellular carcinoma (HCC). In this study, we aim to investigate the roles of HBV on angiogenin (ANG), as well as the effects on cell proliferation in presence of ANG down-regulation. Methods: Serum ANG was determined by ELISA. The expression of ANG mRNA and protein in HCC cell lines with or without HBV/HBx were determined. Western blot and ELISA were conducted to determine the effects of HBV/HBx on IL-6 expression. The role of IL-6 on ANG was evaluated by IL-6 recombinant protein or IL-6 neutralizing antibody. Immunofluorescence staining was used to detect the nuclear translocation of ANG. MTT was performed to evaluate the relative inhibition ratio. Result: In vivo experiments showed elevation of serum ANG in patients infected with HBV. In vitro experiments showed HBV and HBx contributed to the transcription and translation of ANG. ANG expression showed increase after IL-6 stimulation, and ANG protein decreased in the presence of IL-6 blocking with its antibody. HBV promoted nuclear translocation of ANG. Inhibiting ANG expression or blocking of nuclear transfer of ANG attenuated the 45S rRNA synthesis and cell proliferation. Conclusion: HBV and HBx protein can increase the level of ANG through IL-6. HBV and HBx contributed to the nuclear translocation of ANG. Cell proliferation was inhibited after inhibiting the expression or nuclear transfer of ANG.

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Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C

Cited by 131 publications

References 37 publications

Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection

Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection

Three decades of research on angiogenin: a review and perspective

HBV Facilitated Hepatocellular Carcinoma Cells Proliferation by Up-Regulating Angiogenin Expression Through IL-6

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