Copy number variation in tRNA isodecoder genes impairs mammalian development and balanced translation (RNA-seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA927106 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23352145_1.fastq.gz | Fastqsanger.gz | |||
| SRR23352145_2.fastq.gz | Fastqsanger.gz | |||
| SRR23352146_1.fastq.gz | Fastqsanger.gz | |||
| SRR23352146_2.fastq.gz | Fastqsanger.gz | |||
| SRR23352147_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 96 |
Similar Datasets
Project description:Copy number variation in tRNA isodecoder genes impairs mammalian development and balanced translation
| PRJNA944705 | ENA
Project description:Copy number variation in tRNA isodecoder genes impairs mammalian development and balanced translation [ATAC-seq]
| PRJNA826758 | ENA
Project description:The number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-Seq, RNA-seq and proteomics we observed distinct molecular consequences of individual tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoder genes buffer the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least six tRNA-Phe alleles is required for embryonic viability and tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA genes is required to buffer translation and viability in mammals.
2023-03-05 | GSE200783 | GEO
Project description:The number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-Seq, RNA-seq and proteomics we observed distinct molecular consequences of individual tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoder genes buffer the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least six tRNA-Phe alleles is required for embryonic viability and tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA genes is required to buffer translation and viability in mammals.
2023-03-05 | GSE223662 | GEO
Project description:The number of tRNA isodecoder genes has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-seq, RNA-seq and proteomics we observed distinct molecular consequences of individual tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoders compensate for the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least four tRNA-Phe isodecoders is required for embryonic development and survival. The loss of tRNA-Phe-1-1 and any other three tRNA-Phe genes causes embryonic lethality indicating that tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA isodecoder genes is required to buffer translation and viability in mammals.
2023-04-19 | PXD029684 | Pride
Project description:The number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-Seq, RNA-seq, ribo-profiling and proteomics we observed distinct molecular consequences of single tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoder genes buffer the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least six tRNA-Phe alleles is required for embryonic viability and tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA genes is required to buffer translation and viability in mammals.
| S-EPMC10113395 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-03-17 | GSE227363 | GEO
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: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: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