tRNA 3′ shortening by LCCR4 as a response to stress in <i>Trypanosoma brucei</i>

Cristodero, Marina; Brogli, Rebecca; Joss, Oliver; Schimanski, Bernd; Schneider, André; Polacek, Norbert

doi:10.1093/nar/gkaa1261

Cited by 9 publications

(6 citation statements)

References 61 publications

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“…Whilst the relative affinities of EF-Tu for Balon and aminoacyl tRNA are unknown, the observation of EF-Tu bound to Balon in our cryo-EM maps implies that they are at least somewhat comparable. Various stress and starvation conditions are known to decrease the availability of aminoacylated tRNAs, which are the primary binding partners of EF-Tu [70][71][72] . Therefore, it is plausible that, under these conditions, greater amounts of free EF-Tu would become available for association with Balon, facilitating its delivery to ribosomes.…”

Section: Ef-tu As a Factor Of Stress Responsementioning

confidence: 99%

A bacterial ribosome hibernation factor with evolutionary connections to eukaryotic protein synthesis

Helena-Bueno

Ekemezie

Brown

et al. 2022

Preprint

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During starvation and stress, virtually all organisms arrest their protein synthesis and convert their ribosomes into a state of dormancy in which a special class of proteins, known as hibernation factors, protect the ribosome from damage. In bacteria, two major families of hibernation factors have been characterized, but the low conservation of these proteins and the huge diversity of species, habitats and environmental stressors has made the discovery of new dormancy factors challenging. In this study, we identify a new bacterial protein involved in ribosome dormancy. We first characterize dormant ribosomes following cold shock in the psychrophilic bacterium Psychrobacter urativorans using proteomics and cryo-EM. We show that during cold shock, ribosomes in this organism associate with a previously uncharacterized protein that occupies ribosomal active centres and multiple drug-binding sites. Our structure reveals that this new factor, which we term Balon, bears no resemblance to known bacterial hibernation factors. Instead, it belongs to a family of bacterial homologs of the eukaryotic translation factor aeRF1. We identify unique motifs present only in Balon but not its archaeal or eukaryotic counterparts that allow it to engage with the peptidyl transferase center and decoding center of dormant bacterial ribosomes. We then show that, across the bacterial kingdom, Balon-encoding genes are found in nearly 20% of known species and are located in operons involved in different types of stress responses, including osmotic and thermal shock, hypoxia, acid, tRNA damage and antibiotic stress. Taken together, our work shows that bacterial cells possess a functional homolog of eukaryotic translation termination factor, which is likely repurposed into a stress-response protein. This finding illuminates a long-sought evolutionary connection between the bacterial and eukaryotic protein synthesis machinery.

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Section: Ef-tu As a Factor Of Stress Responsementioning

confidence: 99%

A bacterial ribosome hibernation factor with evolutionary connections to eukaryotic protein synthesis

Helena-Bueno

Ekemezie

Brown

et al. 2022

Preprint

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“…As tRNAs are the mediator of protein translation, it is not surprising that a common stress response is the alteration of the cellular tRNA pools. tRNA 3’ end trimming is a known mechanism in Trypanosoma brucei , by which the organism makes tRNAs unable to perform the translation in response to stress [ 89 ]. In humans, tRNA fragmentation can be caused by oxidative stress [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology

Fazio

Gullerová

2023

Br J Cancer

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Transfer RNAs (tRNAs) are small non-coding RNAs (sncRNAs) essential for protein translation. Emerging evidence suggests that tRNAs can also be processed into smaller fragments, tRNA-derived small RNAs (tsRNAs), a novel class of sncRNAs with powerful applications and high biological relevance to cancer. tsRNAs biogenesis is heterogeneous and involves different ribonucleases, such as Angiogenin and Dicer. For many years, tsRNAs were thought to be just degradation products. However, accumulating evidence shows their roles in gene expression: either directly via destabilising the mRNA or the ribosomal machinery, or indirectly via regulating the expression of ribosomal components. Furthermore, tsRNAs participate in various biological processes linked to cancer, including apoptosis, cell cycle, immune response, and retroviral insertion into the human genome. It is emerging that tsRNAs have significant therapeutic potential. Endogenous tsRNAs can be used as cancer biomarkers, while synthetic tsRNAs and antisense oligonucleotides can be employed to regulate gene expression. In this review, we are recapitulating the regulatory roles of tsRNAs, with a focus on cancer biology.

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“…Processing of CCA-termini of tRNAs is well-known mechanism for tRNA quality control in E. coli [reviewed in ( Wellner et al, 2018 )]. In addition, it has been recently reported that CCA-termini of tRNAs are shortened under nutritional stress in Trypanosoma brucei ( Cristodero et al, 2021 ). Under stress condition, tRNAs are trimmed by nuclease LCCR4 resulting in translational repression, and repaired quickly once normal condition is restored ( Cristodero et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, it has been recently reported that CCA-termini of tRNAs are shortened under nutritional stress in Trypanosoma brucei ( Cristodero et al, 2021 ). Under stress condition, tRNAs are trimmed by nuclease LCCR4 resulting in translational repression, and repaired quickly once normal condition is restored ( Cristodero et al, 2021 ). However, whether such mechanisms exist in human cells is still unclear because the data concerning ANG-mediated CCA-cleavage are based largely on in vitro experiments ( Czech et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases

Akiyama

Lyons

Fay

et al. 2022

Front. Mol. Biosci.

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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. In addition to cleaving tRNA anticodon loops, ANG has been shown to cleave 3′-CCA termini of tRNAs in vitro, although it is not known whether this process occurs in cells. It has also been suggested that tiRNAs can be generated independently of ANG, although the role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we examined the involvement of ANG in stress-induced tRNA cleavage by focusing on its cleavage of CCA-termini as well as anticodon loops. We show that ANG is not responsible for CCA-deactivation under sodium arsenite (SA) treatment in cellulo, and although ANG treatment significantly increases 3′-tiRNA levels in cells, the majority of 3′-tiRNAs retain their 3′-CCA termini. Instead, other RNases can cleave CCA-termini in cells, although with low efficiency. Moreover, in the absence of ANG, other RNases are able to promote the production of tiRNAs in cells. Depletion of RNH1 (an endogenous inhibitor of RNase A superfamily) promotes constitutively-produced tiRNAs and CCA-deactivated tRNAs in cells. Interestingly, SA treatment in RNH1-depleted cells did not increase the amount of tiRNAs or CCA-deactivated tRNAs, suggesting that RNase A superfamily enzymes are largely responsible for SA-induced tRNA cleavage. We show that interplay between stress-induced RNases cause targeting tRNAs in a stress-specific manner in cellulo.

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tRNA 3′ shortening by LCCR4 as a response to stress in Trypanosoma brucei

Cited by 9 publications

References 61 publications

A bacterial ribosome hibernation factor with evolutionary connections to eukaryotic protein synthesis

A bacterial ribosome hibernation factor with evolutionary connections to eukaryotic protein synthesis

An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology

Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases

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