Toward an Understanding of Extracellular tRNA Biology

Torres, Adrián Gabriel; Martı́, Eulàlia

doi:10.3389/fmolb.2021.662620

Cited by 19 publications

(18 citation statements)

References 124 publications

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“…Finally, it remains possible that the abundance of certain tDRs may reflect not selective biogenesis, but increased stability of these fragments in the extracellular compartment compared to others 54 . Together our findings suggest that extracellular tDRs have distinct signatures and sequences that do not simply reflect the stoichiometry of cellular tDRs and support the findings of others that the biogenesis of extracellular tDRs may be distinct from cellular tDRs 24,25,32 .…”

Section: Arm-seq To Identify Cellular and Extracellular Tdrssupporting

confidence: 83%

“…As mediators of intercellular communication, extracellular RNAs (exRNAs) have emerged as promising biomarkers for the diagnosis and prognosis of various diseases from minimally invasive liquid biopsies 23,24 . In addition to high abundance in cells, tDRs also comprise a significantly proportion of the extracellular RNAome 25,26 . This has been documented in multiple human biofluids, including urine, serum, plasma, saliva, and cerebrospinal fluid, and in cell-conditioned medium 24,27,28 .…”

Section: Introductionmentioning

confidence: 99%

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Distinct stress-dependent signatures of cellular and extracellular tRNA-derived small RNAs (tDRs)

Manning

Bagi

et al. 2021

Preprint

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The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may yield novel biomarkers for different diseases, and potentially identify key signaling pathways important for disease progression. tRNAs and tRNA-derived small RNAs (tDRs) comprise one of the most abundant RNA species in cells and have been associated with cellular stress responses. The presence of RNA modifications on tDRs has been an obstacle for accurately identifying tDRs with conventional small RNA sequencing. Here, we use AlkB-facilitated methylation sequencing (ARM-seq) to uncover a comprehensive landscape of cellular and extracellular tDR expression in a variety of human and rat cells during common stress responses, including nutritional deprivation, hypoxia, and oxidative stress. We found that extracellular tDRs have a distinct fragmentation signature with a predominant length of 31-33 nts and a highly specific termination position when compared with intracellular tDRs. Importantly, we found these signatures are better discriminators of different cellular stress responses compared to extracellular miRNAs. Distinct extracellular tDR signatures for each profiled stressor are elucidated in four different types of cells. This distinct extracellular tDR fragmentation pattern is also noted in plasma extracellular RNAs from patients on cardiopulmonary bypass. The observed overlap of these patient tDR signatures with the signatures of nutritional deprivation and oxidative stress in our cellular models provides preliminary in vivo corroboration of our findings and demonstrates the potential to establish novel extracellular tDR biomarkers in human disease models.

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Section: Arm-seq To Identify Cellular and Extracellular Tdrssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Distinct stress-dependent signatures of cellular and extracellular tRNA-derived small RNAs (tDRs)

Manning

Bagi

et al. 2021

Preprint

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“…Cells release tRNA fragments into extracellular medium in many ways (Torres and Martí, 2021). tRNA modifications influence tRNA fragment biogenesis, and the secreted tRNA fragments often match the abundance profiles of those fragments in cells.…”

Section: Discussionmentioning

confidence: 99%

Profiling Selective Packaging of Host RNA and Viral RNA Modification in SARS-CoV-2 Viral Preparations

Peña

Zhang

Halucha

et al. 2022

Front. Cell Dev. Biol.

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Viruses package host RNAs in their virions which are associated with a range of functions in the viral life cycle. Previous transcriptomic profiling of host RNA packaging mostly focused on retroviruses. Which host RNAs are packaged in other viruses at the transcriptome level has not been thoroughly examined. Here we perform proof-of-concept studies using both small RNA and large RNA sequencing of six different SARS-CoV-2 viral isolates grown on VeroE6 cells to profile host RNAs present in cell free viral preparations and to explore SARS-CoV-2 genomic RNA modifications. We find selective enrichment of specific host transfer RNAs (tRNAs), tRNA fragments and signal recognition particle (SRP) RNA in SARS-CoV-2 viral preparations. Different viral preparations contain the same set of host RNAs, suggesting a common mechanism of packaging. We estimate that a single SARS-CoV-2 particle likely contains up to one SRP RNA and four tRNA molecules. We identify tRNA modification differences between the tRNAs present in viral preparations and those in the uninfected VeroE6 host cells. Furthermore, we find uncharacterized candidate modifications in the SARS-CoV-2 genomic RNA. Our results reveal an under-studied aspect of viral-host interactions that may be explored for viral therapeutics.

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“…In contrast, several tDR species were downregulated in response to exercise in HDL particles in nonusers. Torres et al (2021) recently proposed that extracellular tDRs may act as important paracrine signaling molecules whose activity depends on the mechanisms of the release and the capturing of recipient cells (Torres and Marti, 2021). To support this theory, the selective loading of tRNAs has been established in EVs (Chiou et al, 2018;Nolte-'t Hoen et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles and high-density lipoproteins: Exercise and estrogen-responsive small RNA carriers

Karvinen

Korhonen

Sievänen

et al. 2022

Preprint

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Decreased systemic estrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both estrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signaling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that estrogen deficiency caused by menopause blunts acute exercise-induced systemic miR-response in both EV and HDL particles.

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Toward an Understanding of Extracellular tRNA Biology

Cited by 19 publications

References 124 publications

Distinct stress-dependent signatures of cellular and extracellular tRNA-derived small RNAs (tDRs)

Distinct stress-dependent signatures of cellular and extracellular tRNA-derived small RNAs (tDRs)

Profiling Selective Packaging of Host RNA and Viral RNA Modification in SARS-CoV-2 Viral Preparations

Extracellular vesicles and high-density lipoproteins: Exercise and estrogen-responsive small RNA carriers

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