Dietary effects on cytosolic and mitochondrial tRNA abundance and modification patterns across mouse tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE300004 | GEO | 2026/06/16
REPOSITORIES: GEO
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| GSE300004_readcounts.tsv.gz | Tabular |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:Transfer RNAs (tRNAs) and their derived small RNAs (tDRs) vary across mammalian tissues, but the . We applied Ordered Two-Template Relay sequencing (OTTR-seq) to profile small RNAs in 19 tissues from adult mice, quantifying mature tRNAs and tDRs at isodecoder resolution and inferring select base‑modification signatures from reverse‑transcriptase misincorporations. We observe tissue‑biased expression of many isodecoders and identify tDRs with greater tissue specificity than their parent tRNAs. Modification‑associated mismatch profiles are largely consistent across tissues, with notable isodecoder‑specific differences at canonical sites (e.g., A34→I, G37→m1G/wybutosine, C47d→m3C). Because RT‑based signatures do not capture all modifications without chemical pretreatments, our modification inferences represent a subset of the tRNA epitranscriptome. These data provide an isodecoder‑resolved reference for tissue‑biased tRNA and tDR regulation in mice and a framework for exploring disease‑associated remodeling of the tRNA pool. Recent studies have begun to illustrate that transfer RNA (tRNA) expression, processing, and modification can vary among different mammalian tissues and cell types. The full scope of these differences and the regulatory mechanisms that modulate production of a wide variety of tRNAs and tDRs (tRNA-derived small RNAs) across tissues, cell types, and changing cellular conditions is poorly understood. Dysregulation of these transcripts has increasingly been implicated as a critical factor in disease progression; thus, a deeper understanding of the homeostatic variance across somatic tissues is vital. Here, we systematically profile the relative changes in abundance and key sites of base modification within tRNAs, tDRs, and other small RNAs using a powerful small RNA sequencing method, Ordered Two-Template Relay sequencing (OTTR-seq), across a panel of 19 mouse tissues. By analyzing a diverse range of healthy tissues, we can better recognize tissue-biased regulation of tRNAs and identify tDRs that exhibit significantly greater tissue specificity than their corresponding source tRNAs. Furthermore, we leveraged reverse transcriptase-associated base misincorporations to construct an isodecoder-specific map of select nucleotide modifications across all mouse tRNAs. Differentially modified isodecoders can alter their translation functionality, stability, and basis for production of unique tDR profiles. This dataset provides the most comprehensive view to date of the dynamic relationships between tRNAs, their modifications, and tDRs in a mammalian model, offering an important knowledgebase for understanding tissue-specific regulation and the role of these molecules in disease.
2025-11-01 | GSE309058 | GEO
Project description:The human genome encodes hundreds of tRNA genes but their individual contribution to the tRNA pool is not fully understood. Deep sequencing of tRNA transcripts (tRNA-Seq) can estimate tRNA abundance at single gene resolution, but tRNA structures and post-transcriptional modifications impair these analyses. Here we present a bioinformatics strategy to investigate differential tRNA gene expression and use it to compare tRNA-Seq datasets from cultured human cells and human brain. We find that sequencing caveats affect quantitation of only a subset of human tRNA genes. Unexpectedly, we detect several cases where the differences in tRNA expression among samples do not involve variations at the level of isoacceptor tRNA sets (tRNAs charged with the same amino acid but using different anticodons); but rather among tRNA genes within the same isodecoder set (tRNAs having the same anticodon sequence). Because isodecoder tRNAs are functionally equal in terms of genetic translation, their differential expression may be related to non-canonical tRNA functions. We show that several instances of differential tRNA gene expression result in changes in the abundance of tRNA-derived fragments (tRFs) but not of mature tRNAs. Examples of differentially expressed tRFs include: PIWI-associated RNAs, tRFs present in tissue samples but not in cells cultured in vitro, and somatic tissue-specific tRFs. Our data support that differential expression of tRNA genes regulate non-canonical tRNA functions performed by tRFs.
2019-04-17 | GSE114904 | GEO
Project description:Queuosine (Q) is a conserved tRNA modification at the wobble anticodon position of tRNAs that read the codons of amino acids Tyr, His, Asn, and Asp. Q-modification in tRNA plays important roles in the regulation of translation efficiency and fidelity. Queuosine tRNA modification is synthesized de novo in bacteria, whereas the substrate for Q-modification in tRNA in mammals is queuine, the catabolic product of the Q-base of gut bacteria. This gut microbiome dependent tRNA modification may play pivotal roles in translational regulation in different cellular contexts, but extensive studies of Q-modification biology are hindered by the lack of high throughput sequencing methods for its detection and quantitation. Here, we describe a periodate-treatment method of biological RNA samples that enables single base resolution profiling of Q-modification in tRNAs by Nextgen sequencing. Periodate oxidizes the Q-base, which results in specific deletion signatures in the RNA-seq data. Unexpectedly, we found that periodate-treatment also enables the detection of several 2-thio-modifications including τm5s2U, mcm5s2U, cmnm5s2U, and s2C by sequencing in human and E. coli tRNA. We term this method Periodate-dependent analysis of queuosine and thio modification sequencing (PAQS-seq). We assess Q- and 2-thio-modifications at the tRNA isodecoder level, and 2-thio modification changes in stress response. PAQS-seq should be widely applicable in the biological studies of Q- and 2-thio-modifications in mammalian and microbial tRNAs.
2022-06-22 | GSE196016 | GEO
Project description:Deep sequencing of tRNAs have historically been nutoriously difficult. Here, we benchmark a newly developed library prep protocol termed OTTR agains intact tRNAs as well as tRNA fragments and show that OTTR outperforms any other commercial cloning protocol.
2022-03-06 | GSE197651 | GEO
Project description:Transfer RNAs (tRNA) are quintessential in deciphering the genetic code; disseminating nucleic acid triplets into correct amino acid identity. While this decoding function is clear, an emerging theme is that tRNA abundance and functionality can powerfully impact protein production rate, folding, activity, and messenger RNA stability. Importantly, however, the expression pattern of tRNAs (in even simple systems) is obliquely known. Limited analysis suggests tRNA levels change during proliferation, differentiation, cancer, and neurodegeneration; possibly mediating changes in translation efficiency and mRNA stability. A major limitation for the field has been the ability to subject tRNA pools to high-throughput analysis as they are highly structured, modified, and of high sequence similarity. Here we present Quantitative Mature tRNA sequencing (QuantM-tRNA seq), an easily implemented high-throughput technique to monitor tRNA abundance and sequence variants (possibly due to RNA modifications). With QuantM-tRNA seq we provide a comprehensive analysis of the tRNA transcriptome from distinct mammalian tissues. We observe dramatic distinctions in isodecoder expression and likely RNA modifications between unique tissues with a particularly strong signature within the central nervous system. Remarkably, despite dramatic changes in tRNA isodecoder gene expression, the overall anticodon pool of each tRNA family is similar. These findings suggest that anticodon pools are buffered via an unknown mechanism to achieve uniform decoding throughout the body.
2020-08-04 | GSE141436 | GEO
Project description:tRNA fragments (tRFs) are natural, small non-coding RNAs produced by endogenous ribonucleolytic cleavage of tRNAs. tRFs play a role in many biological pathways including regulation of cell proliferation. Specific modifications also affect tRF abundance and the abundance of their cognate, full-length tRNA. Queuosine (Q) modification occurs at the wobble anticodon nucleotide of 4 mammalian tRNAs and protects these tRNAs from fragmentation. Here, we investigated cell-type and tRNA Q-modification-dependences on cell proliferation. We found that Q-modified tRNA can either increase, decrease, or make no difference on proliferation. Among the six cell lines tested, proliferation only decreased in MCF7, a breast cancer cell line, when tRNAs were Q-modified, but the proliferation can be restored by the transfection of Q-modification-dependent tRFHis. tRNA-seq showed that in MCF7 cells, tRNA Q-modification reduced m1A58 and m3C32 modification levels, consistent with reduced translation. Additionally, polysome profiling showed a Q-modification associated codon usage pattern that corresponded with altered translation efficiency of ribosomal proteins required for faster proliferation. Protein pull-down using tRFHis identified Musashi RNA binding protein 2 (Msi2) as a tRFHis binding protein. Msi2 is known to enhance mitochondrial activities, and Msi2 knockdown reduced the tRFHis dependent cell proliferation effect. Our results illustrate a highly cell-type dependent proliferation effect of tRNA Q-modification, suggesting multi-faceted mechanisms in studying this ubiquitous tRNA modification.
2026-03-31 | GSE293476 | GEO
Project description:tRNA fragments (tRFs) are natural, small non-coding RNAs produced by endogenous ribonucleolytic cleavage of tRNAs. tRFs play a role in many biological pathways including regulation of cell proliferation. Specific modifications also affect tRF abundance and the abundance of their cognate, full-length tRNA. Queuosine (Q) modification occurs at the wobble anticodon nucleotide of 4 mammalian tRNAs and protects these tRNAs from fragmentation. Here, we investigated cell-type and tRNA Q-modification-dependences on cell proliferation. We found that Q-modified tRNA can either increase, decrease, or make no difference on proliferation. Among the six cell lines tested, proliferation only decreased in MCF7, a breast cancer cell line, when tRNAs were Q-modified, but the proliferation can be restored by the transfection of Q-modification-dependent tRFHis. tRNA-seq showed that in MCF7 cells, tRNA Q-modification reduced m1A58 and m3C32 modification levels, consistent with reduced translation. Additionally, polysome profiling showed a Q-modification associated codon usage pattern that corresponded with altered translation efficiency of ribosomal proteins required for faster proliferation. Protein pull-down using tRFHis identified Musashi RNA binding protein 2 (Msi2) as a tRFHis binding protein. Msi2 is known to enhance mitochondrial activities, and Msi2 knockdown reduced the tRFHis dependent cell proliferation effect. Our results illustrate a highly cell-type dependent proliferation effect of tRNA Q-modification, suggesting multi-faceted mechanisms in studying this ubiquitous tRNA modification.
2026-03-31 | GSE293473 | GEO
Project description:tRNAs are important regulators of protein synthesis, and dysregulation of their abundance and modifications status is involved in many human diseases, including cancer. Despite the rapid development of novel tRNA sequencing approaches, due to tRNAs stable secondary structure and abundant modification sites, human tRNA landscape has remained mostly unexplored. Here, we evaluated the new nanopore RNA004 chemistry that is combined with an upgraded Dorado RNA base-caller model for tRNA quantification and site-specific modification determination in human cancer models. We demonstrate that this technology is sensitive to changes in tRNA expression between cancer cell types and response to external stress conditions, with highly reproducible results. We also show that analysis of base-calling error rate confirms the presence of known modifications, among them is the cancer-associated tRNAPhe-Wybutosine modification by TRMT12 (TYW2) . Furthermore, utilizing the new feature of RNA004 chemistry for the detection of common modifications, we show site-specific identification of m5C and pseudouridine at their annotated positions as well as in their known tRNA isoacceptors. We also reveal unique new modification sites and pinpoint a possible limitation of this method in differentiating between m1A and m6A chemical isomers. Overall, RNA004 tRNA-seq has the potential to improve human tRNAome characterization of tRNA abundance and site-specific modifications simultaneously.
2025-12-02 | GSE291699 | GEO
Project description:Transfer RNAs (tRNAs) are fundamental for both cellular and viral gene expression during viral infection. Moreover, mounting evidence supports a noncanonical role for tRNA cleavage products in the control of gene expression during diverse conditions of stress and infection. We previously reported that infection with the model murine gammaherpesvirus, MHV68, leads to altered tRNA transcription, suggesting that tRNA regulation may play an important role in mediating viral replication or the host response. To better understand how viral infection alters tRNA expression, we combined Ordered Two Template Relay (OTTR) with tRNA-specific bioinformatic software called tRAX to profile full-length tRNAs and fragmented tRNA-derived RNAs (tDRs) during infection with the model gammaherpesvirus, MHV68. We find that OTTR-tRAX is a powerful sequencing strategy for combined tRNA/tDR profiling, and reveal that MHV68 infection triggers pre-tRNA and mature tRNA cleavage, resulting in the accumulation of specific tDRs. Fragments of virally-encoded tRNAs (virtRNAs), as well as virtRNA base modification signatures are also detectable during infection. We further dissected the biogenesis pathway of an MHV68-induced cleavage product from a pre-tRNA. Our data shows that pre-tDR-Tyr expression is dependent on the tRNA splicing factor, TSEN2, and that pre-tDR-Tyr expression is inhibited by the kinase, CLP1, which regulates tRNA splicing. Significantly, our findings suggest that CLP1 kinase is required for infectious gammaherpesvirus production, offering new insight into the importance of tRNA processing during viral infection.
2024-07-31 | GSE255627 | GEO
Project description:Post-transcriptional modifications are important for transfer RNAs (tRNAs) to be efficient and accurate in translation on the ribosome. The m1G37 modification on a subset of tRNAs in bacteria are generated by a conserved methyltransferase TrmD and is essential for bacterial growth. Previous studies showed that m1G37 has an important role in preventing translational frameshifting and also that this modification is coupled with aminoacylation of tRNAs for proline. Here we performed suppressor screening to isolate a mutant E. coli cell that lacks TrmD but is viable, and the whole-genome sequencing revealed several mutations on prolyl-tRNA synthetase (ProRS) gene conferring cell viability in the absence of TrmD. Biochemical assays confirmed uncoupling of m1G37 modification and aminoacylation, and cell-based assays uncovered the critical role of m1G37 in supporting Wobble decoding.
2022-09-24 | E-MTAB-12178 | biostudies-arrayexpress