The regulatory world of tRNA fragments beyond canonical tRNA biology

Polacek, Norbert; Ivanov, Pavel

doi:10.1080/15476286.2020.1785196

Cited by 15 publications

(8 citation statements)

References 27 publications

(27 reference statements)

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“…Interestingly, several tRNA-derived RNA fragments (tRFs) were enriched in the stationary phase ( Figure 3 a and Figure 4 a). Recently, tRFs have gained vast recognition as regulatory molecules in all three domains of life [ 51 ]. tRFs appear to be involved in a wide range of biological roles, including the regulation of transcription, translation, stress granule formation, apoptosis, cell proliferation, tumor suppression, RNAi, vesicle-mediated intercellular communication, intergenerational inheritance, retrotransposons mobility, cell differentiation, and ribosome biogenesis [ 52 , 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-Wide Analysis of Stationary Phase Small ncRNAs in E. coli

Raad

Luidalepp

Fasnacht

et al. 2021

IJMS

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Almost two-thirds of the microbiome’s biomass has been predicted to be in a non-proliferating, and thus dormant, growth state. It is assumed that dormancy goes hand in hand with global downregulation of gene expression. However, it remains largely unknown how bacteria manage to establish this resting phenotype at the molecular level. Recently small non-protein-coding RNAs (sRNAs or ncRNAs) have been suggested to be involved in establishing the non-proliferating state in bacteria. Here, we have deep sequenced the small transcriptome of Escherichia coli in the exponential and stationary phases and analyzed the resulting reads by a novel biocomputational pipeline STARPA (Stable RNA Processing Product Analyzer). Our analysis reveals over 12,000 small transcripts enriched during both growth stages. Differential expression analysis reveals distinct sRNAs enriched in the stationary phase that originate from various genomic regions, including transfer RNA (tRNA) fragments. Furthermore, expression profiling by Northern blot and RT-qPCR analyses confirms the growth phase-dependent expression of several enriched sRNAs. Our study adds to the existing repertoire of bacterial sRNAs and suggests a role for some of these small molecules in establishing and maintaining stationary phase as well as the bacterial stress response. Functional characterization of these detected sRNAs has the potential of unraveling novel regulatory networks central for stationary phase biology.

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Section: Discussionmentioning

confidence: 99%

Transcriptome-Wide Analysis of Stationary Phase Small ncRNAs in E. coli

Raad

Luidalepp

Fasnacht

et al. 2021

IJMS

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“…Originally described as rather passive adaptor molecules involved in translation, tRNAs and especially tRNA-derived RNAs have been shown recently to play roles in a plethora of additional cellular functions ( 59 , 60 ). In particular, tRNA halves and fragments have been described in all kingdoms of life and were also shown to promote survival in cells exposed to non-favorable environmental conditions ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

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

Cristodero

Brogli

Joss

et al. 2021

Nucleic Acids Research

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Sensing of environmental cues is crucial for cell survival. To adapt to changes in their surroundings cells need to tightly control the repertoire of genes expressed at any time. Regulation of translation is key, especially in organisms in which transcription is hardly controlled, like Trypanosoma brucei. In this study, we describe the shortening of the bulk of the cellular tRNAs during stress at the expense of the conserved 3′ CCA-tail. This tRNA shortening is specific for nutritional stress and renders tRNAs unsuitable substrates for translation. We uncovered the nuclease LCCR4 (Tb927.4.2430), a homologue of the conserved deadenylase Ccr4, as being responsible for tRNA trimming. Once optimal growth conditions are restored tRNAs are rapidly repaired by the trypanosome tRNA nucleotidyltransferase thus rendering the recycled tRNAs amenable for translation. This mechanism represents a fast and efficient way to repress translation during stress, allowing quick reactivation with a low energy input.

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“…When calculating TE, we determined AA supply from the usage of all tRNA genes charged with the same AA and calculated AA demand by weighting the AA gene usages by their expression for all cell types. From the AA supply side, it is oversimplistic to assume that all tRNAs will necessarily function in translation elongation, especially since tRNAs are known to perform an array of different roles, including as tRNA-derived fragments (Polacek and Ivanov 2020). From the AA demand side, different protein isoforms are known to exist across cell types.…”

Section: Discussionmentioning

confidence: 99%

Analysis at single-cell resolution identifies a stable mammalian tRNA-mRNA interface and increased translation efficiency in neurons

Gao

Kutter

2021

Preprint

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The correlation between codon and anticodon pools influences the efficiency of translation, but whether differences exist in these pools across individual cells is unknown. We determined that codon usage and amino acid demand are highly stable across different cell types using single-cell RNA-sequencing atlases of adult mouse and fetal human. After demonstrating the robustness of ATAC-sequencing for analysis of tRNA gene usage, we quantified anticodon usage and amino acid supply in adult mouse and fetal human single-cell ATAC-seq atlases. We found that tRNA gene usage is overall coordinated across cell types, except in neurons which clustered separately from other cell types. Integration of these datasets revealed a strong and statistically significant correlation between amino acid supply and demand across almost all cell types. Neurons have an enhanced translation efficiency over other cell types, driven by an increased supply of Ala-AGC anticodons. This results in faster decoding of the Ala-GCC codon, as determined by cell-type specific ribosome profiling, and a reduction of Ala-AGC anticodon pools may be implicated in neurological pathologies. This study, the first such examination of codon usage, anticodon usage, and translation efficiency at single-cell resolution, identifies conserved features of translation elongation across mammalian cellular diversity and evolution.

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The regulatory world of tRNA fragments beyond canonical tRNA biology

Cited by 15 publications

References 27 publications

Transcriptome-Wide Analysis of Stationary Phase Small ncRNAs in E. coli

Transcriptome-Wide Analysis of Stationary Phase Small ncRNAs in E. coli

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

Analysis at single-cell resolution identifies a stable mammalian tRNA-mRNA interface and increased translation efficiency in neurons

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