ANG cleaves tRNA to yield tRNA halves

Stable Identifier
R-HSA-9708327
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Angiogenin (ANG) cleaves within or near the anticodon of specific tRNAs including but not limited to: tRNA Arg ACG (Fu et al. 2009), tRNA Arg CCG (Fu et al. 2009), tRNA Glu CTC (Fu et al. 2009), tRNA Gly CCC (Fu et al. 2009), tRNA Gly GCC (Fu et al. 2009), tRNA Met CAT (Fu et al. 2009, Su et al. 2019), tRNA Pro AGG (Yamasaki et al. 2009), tRNA Pro TGG (Yamasaki et al. 2009), tRNA Val AAC (Fu et al. 2009), tRNA Ala AGC (Su et al. 2019), tRNA Ala CGC (Su et al. 2019), tRNA Ala TGC (Su et al. 2019), tRNA Asp GTC (Su et al. 2019), tRNA Glu TTC (Su et al. 2019), tRNA His GTG (Su et al. 2019), tRNA Leu CAG (Su et al. 2019), tRNA Leu TAG (Su et al. 2019), tRNA Lys TTT (Su et al. 2019), tRNA Ser GCT (Su et al. 2019), tRNA Ser CGA (Su et al. 2019), tRNA Val CAC (Su et al. 2019), tRNA Val TAC (Su et al. 2019) (also Lee and Vallee 1989, Saxena et al. 1992, Emara et al. 2010, Ivanov et al. 2011). The products are a 5' fragment of about 30-35 nt and a 3' fragment of about 40 nt known as tRNA halves or stress-induced tRNA fragments (tiRNAs) (Emara et al. 2010). As a result of ANG cleavage, the 5’ tRNA halves contain 5' monophosphates (Emara et al. 2010) and 3' cyclic monophosphates (Shigematsu et al. 2018), while the 3’ tRNA halves contain 5' hydroxyl groups (Shigematsu et al., 2018). ANG cleaves tRNA in response to biological conditions such as exposure to sex hormones and stresses such as starvation, oxidative stress, and virus infection (Fu et al. 2009, Emara et al. 2010, Ivanov et al. 2011, Wang et al. 2013, Honda et al. 2015, Selitsky et al. 2015), but several tRNA halves are still produced after stress in ANG knockout cells (Su et al. 2020). The 5' tiRNAs inhibit translation by displacing eIF4F from the m(7)G caps of mRNAs (Emara et al. 2010, Ivanov et al. 2011). The 3’ tiRNAs protect cells against stress-induced apoptosis by interacting with cytochrome C (inferred from mouse homologs in Saikia et al, 2014). The products of ANG have modifications present on mature tRNAs (Drino et al. 2020); therefore, the cleavage is believed to occur in the cytosol (Yamasaki et al. 2009, reviewed in Lyons et al. 2018) perhaps as ANG is translocated from receptors on the plasma membrane through the cytosol to the nucleus.

Literature References
PubMed ID Title Journal Year
25567797 Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C

Selitsky, SR, Baran-Gale, J, Honda, M, Yamane, D, Masaki, T, Fannin, EE, Guerra, B, Shirasaki, T, Shimakami, T, Kaneko, S, Lanford, RE, Lemon, SM, Sethupathy, P

Sci Rep 2015
1400510 Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily

Saxena, SK, Rybak, SM, Davey, RT, Youle, RJ, Ackerman, EJ

J Biol Chem 1992
31582561 Angiogenin generates specific stress-induced tRNA halves and is not involved in tRF-3-mediated gene silencing

Su, Z, Kuscu, C, Malik, A, Shibata, E, Dutta, A

J Biol Chem 2019
19114040 Stress induces tRNA cleavage by angiogenin in mammalian cells

Fu, H, Feng, J, Liu, Q, Sun, F, Tie, Y, Zhu, J, Xing, R, Sun, Z, Zheng, X

FEBS Lett 2009
26124144 Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

Honda, S, Loher, P, Shigematsu, M, Palazzo, JP, Suzuki, R, Imoto, I, Rigoutsos, I, Kirino, Y

Proc Natl Acad Sci U S A 2015
21855800 Angiogenin-induced tRNA fragments inhibit translation initiation

Ivanov, P, Emara, MM, Villén, J, Gygi, SP, Anderson, P

Mol Cell 2011
20129916 Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly

Emara, MM, Ivanov, P, Hickman, T, Dawra, N, Tisdale, S, Kedersha, N, Hu, GF, Anderson, P

J Biol Chem 2010
2730651 Characterization of ribonucleolytic activity of angiogenin towards tRNA

Lee, FS, Vallee, BL

Biochem Biophys Res Commun 1989
32138588 Production and purification of endogenously modified tRNA-derived small RNAs

Drino, A, Oberbauer, V, Troger, C, Janisiw, E, Anrather, D, Hartl, M, Kaiser, S, Kellner, S, Schaefer, MR

RNA Biol 2020
23183536 Identification and functional characterization of tRNA-derived RNA fragments (tRFs) in respiratory syncytial virus infection

Wang, Q, Lee, I, Ren, J, Ajay, SS, Lee, YS, Bao, X

Mol Ther 2013
19332886 Angiogenin cleaves tRNA and promotes stress-induced translational repression

Yamasaki, S, Ivanov, P, Hu, GF, Anderson, P

J Cell Biol 2009
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Catalyst Activity

endoribonuclease activity of ANG [cytosol]

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