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tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9708296

PubChem

R-HSA-9708296

Description

Defined fragments of tRNAs, termed tRNA‑derived small RNAs (tsRNAs), have been observed in particular cell types and in response to biological conditions such as exposure to sex hormone or stresses such as hypoxia, starvation, oxidative stress, and virus infection (reviewed in Keam and Hutvagner 2015, Kumar et al. 2016, Oberbauer and Schaefer 2018, Park et al. 2020, Su et al. 2020, Xie et al. 2020, Zhu et al. 2020). Rather than being the random products of tRNA degradation, tsRNAs appear to be the specific products of ribonucleases. Two categories of tRNA‑derived small RNAs (tsRNAs) have been described: (1) longer (31‑40nt) tsRNAs known as tRNA halves or stress‑induced tsRNAs (tiRNAs) that are produced by single cleavage of tRNAs within or near the anticodon and (2) shorter (15‑30 nt) tsRNAs termed tRNA-related fragments (tRFs) that result from cleavage closer to the 5' or 3' end of the tRNA. tRF-3s are derived from the 3' region of the tRNA, approximately the region from the T loop to the 3' terminus. tRF-5s are derived from the 5' region of the tRNA, approximately the region from the D loop to the 5' terminus. tRF2‑type tRFs (also called internal tRFs) are derived from the central region of the tRNA, approximately the region between the D loop and the T loop and containing the anticodon. tRF-1s, also known as Type II tRFs or 3’U tRFs, are the 3' trailers of particular tRNAs that persist after processing.
In most cases the enzymes responsible for the cleavages are not yet known, however several ribonucleases involved in cleavage of tRNA have been identified: the secreted and endocytosed ribonuclease A family members angiogenin (ANG) and RNase 1; the interferon-induced ribonucleases RNase L, Schlafen 11 (SLFN11) and Schlafen13 (SLFN13 or RNase S13); the cytosolic ribonuclease III‑like (double strand RNA‑specific) enzyme DICER1; and the RNA processing enzyme ELAC2. ANG is secreted, binds receptors on cell membranes, is endocytosed, and translocates to the nucleus. ANG cleaves within the anticodon loop to produce tRNA halves and the cleavage is thought to occur while ANG is transiently located in the cytosol (Lee and Vallee 1989, Saxena et al. 1992, Fu et al. 2009, Yamasaki et al. 2009, Emara et al. 2010, Ivanov et al. 2011). Cleavage by ANG is observed in response to cellular stresses such as starvation (Fu et al. 2009, Yamasaki et al. 2009, Emara et al. 2010, Ivanov et al. 2011). However, ANG knockout cells continue to produce stress-induced tRNA halves, suggesting that other enzymes are also involved in producing the halves (Su et al. 2019). Similar to ANG as an RNase A member, the secreted endoribonuclease RNase 1 cleaves tRNAs at the anticodon loop in the extracellular space (Nechooshtan et al. 2020).
Interferon-induced RNases can also cleave tRNAs. RNase L is responsive to double stranded RNAs and cleaves at the tRNA anticodon loop (Donovan et al. 2017). Schlafen family members SLFN11 and SLFN13 can also cleave tRNAs (Li et al. 2018, Yang et al. 2018).
DICER1 cleaves double‑stranded regions of tRNAs near the 5' terminus or 3' terminus to produce short tRFs (Cole et al. 2009, Yeung et al. 2009, Maute et al. 2013, Hasler et al. 2016). The mechanism that dissociates the double‑stranded products of DICER1 to yield single‑stranded tRFs may be the same as that for miRNAs, but this has not yet been demonstrated. Furthermore, the bulk of the short tRFs is still detected in DICER1-null cells (Kumar 2014, Kuscu & Kumar et al. 2018), suggesting other unknown factors are involved in their biogenesis. ELAC2 in the cytosol cleaves the 3' trailers of precursors of tRNA Ser TGA, tRNA Ser GTC, and tRNA Asp GTC, and tRNA Asp GTC (Lee et al. 2009). The trailers (also called tRF-1s) then persist in the cytosol (Kumar et al. 2014).

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 2** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
Q9BQ52	Zinc phosphodiesterase ELAC protein 2	ELAC2 HPC2	view
Q9UPY3	Endoribonuclease Dicer	DICER DICER1 HERNA KIAA0928	view

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