A tRNA half modulates translation as stress response in Trypanosoma brucei

Fricker, Roger; Brogli, Rebecca; Luidalepp, Hannes; Wyss, Leander; Fasnacht, Michel; Joss, Oliver; Żywicki, Marek; Helm, Mark; Schneider, André; Cristodero, Marina; Polacek, Norbert

doi:10.1038/s41467-018-07949-6

Cited by 112 publications

(134 citation statements)

References 58 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…Biochemical attempts for enriching small RNAs including tsRNA have been published [56]. However, reports that aimed at addressing molecular function or interactions of specific tsRNAs have almost exclusively used synthetic RNA sequences (with published exceptions [57]) thereby largely ignoring the possibility that tsRNA structure and function could be determined by RNA modifications. Theoretically, chemical RNA synthesis allows introducing modified nucleotides at specific positions given that these positions are known once such modification patterns have been determined.…”

Section: Discussionmentioning

confidence: 99%

Production and purification of endogenously modified tRNA-derived small RNAs

et al. 2020

View full text Add to dashboard Cite

2020): Production and purification of endogenously modified tRNA-derived small RNAs, RNA Biology, ABSTRACT During particular stress conditions, transfer RNAs (tRNAs) become substrates of stress-induced endonucleases, resulting in the production of distinct tRNA-derived small RNAs (tsRNAs). These small RNAs have been implicated in a wide range of biological processes, but how isoacceptor and even isodecoder-specific tsRNAs act at the molecular level is still poorly understood. Importantly, stress-induced tRNA cleavage affects only a few tRNAs of a given isoacceptor or isodecoder, raising the question as to how such limited molecule numbers could exert measurable biological impact. While the molecular function of individual tsRNAs is likely mediated through association with other molecules, addressing the interactome of specific tsRNAs has only been attempted by using synthetic RNA sequences. Since tRNAs carry post-transcriptional modifications, tsRNAs are likely modified but the extent of their modifications remains largely unknown. Here, we developed a biochemical framework for the production and purification of specific tsRNAs using human cells. Preparative scale purification of tsRNAs from biological sources should facilitate experimentally addressing as to how exactly these small RNAs mediate the multitude of reported molecular functions. ARTICLE HISTORY

show abstract

Section: Discussionmentioning

confidence: 99%

Production and purification of endogenously modified tRNA-derived small RNAs

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In this study, we tested whether ANG cleaves the 3'-CCA termini of tRNAs in vivo. If ANG efficiently cleaves 3'-CCA termini in vivo, it could contribute to stress-induced translational repression by mechanisms distinct from the reported before, where tRNA fragments directly interact with translational machinery (13,(48)(49)(50)(51)(52). However, our data using RNA-seq reveal that ANG does not affect the percentage of CCA-or CC-terminating species in tRNA fractions, thus demonstrating that ANG does not efficiently cleave 3'-CCA termini in vivo (Fig.…”

Section: Discussionmentioning

confidence: 41%

Multiple ribonuclease A family members cleave transfer RNAs in response to stress

Akiyama

Lyons

Fay

et al. 2019

Preprint

View full text Add to dashboard Cite

During stress, changes in gene expression are critical for cell survival. Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. The role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we show that other members of the RNase A family are capable of targeting tRNAs in stress-responsive manner. We show that in the absence of ANG, these RNases also promote the production of tiRNAs. Moreover, specific stresses (such as treatment with sodium arsenite) activate cleavage of universal 3'-CCA termini of tRNAs in ANG-independent fashion in living cells. We conclude that multiple RNase A family members are capable of targeting tRNAs in a stress-specific manner in vivo.

show abstract

“…In addition, tRNA halves (especially 3' halves) from various tRNAs interact with cytochrome C and protect cells from apoptosis during stress (20). Recently stress-induced 3' half from tRNA Thr in Trypanosoma Brucei has been found to stimulate translation (67). It is highly likely that tRNA halves have divergent functions and many tRNA halves (including the ones we identify from selenocystein) have not been investigated in details.…”

Section: Discussionmentioning

confidence: 99%

The role of ANGIOGENIN, or lack thereof, in the generation of stress-induced tRNA halves and of smaller tRNA fragments that enter Argonaute complexes

Kuscu

Malik

et al. 2019

Preprint

View full text Add to dashboard Cite

Overexpressed Angiogenin (ANG) cleaves tRNA anticodons to produce tRNA halves similar to those produced in response to stress, but it is not clear whether endogenous ANG is essential for producing the stress-induced tRNA halves. It is also not clear whether smaller tRNA fragments (tRFs) are generated from the tRNA halves. Global short RNAseq experiments reveal that ANG overexpression selectively cleaves a subset of tRNAs (tRNA Glu , tRNA Gly , tRNA Lys , tRNA Val , tRNA His , tRNA Asp and tRNA SeC ) to produce tRNA halves and 26-30 bases long tRF-5s. Surprisingly, knockout of ANG reveals that the majority of stress-induced tRNA halves except 5' half from tRNA HisGTG and 3' half from tRNA AspGTC are ANGindependent, suggesting there are other RNases that can produce tRNA halves. The 17-25 bases long tRF-3s and tRF-5s that could enter into Argonaute complexes are not induced by ANG overexpression, suggesting that they are generated independently from tRNA halves. Consistent with this, knockout of ANG did not decrease tRF-3 levels or gene-silencing activity. Therefore ANG cleaves specific tRNAs, is not the only RNAse that creates tRNA halves and the shorter tRFs are not generated from the tRNA halves or from independent tRNA cleavage by ANG.

show abstract

A tRNA half modulates translation as stress response in Trypanosoma brucei

Cited by 112 publications

References 58 publications

Production and purification of endogenously modified tRNA-derived small RNAs

Production and purification of endogenously modified tRNA-derived small RNAs

Multiple ribonuclease A family members cleave transfer RNAs in response to stress

The role of ANGIOGENIN, or lack thereof, in the generation of stress-induced tRNA halves and of smaller tRNA fragments that enter Argonaute complexes

Contact Info

Product

Resources

About