Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transfer RNA-Derived Fragments and isomiRs Are Novel Components of Chronic TBI-Induced Neuropathology.

ABSTRACT: Neuroinflammation is a secondary injury mechanism that evolves in the brain for months after traumatic brain injury (TBI). We hypothesized that an altered small non-coding RNA (sncRNA) signature plays a key role in modulating post-TBI secondary injury and neuroinflammation. At 3threemonths post-TBI, messenger RNA sequencing (seq) and small RNAseq were performed on samples from the ipsilateral thalamus and perilesional cortex of selected rats with a chronic inflammatory endophenotype, and sham-operated controls. The small RNAseq identified dysregulation of 2 and 19 miRNAs in the thalamus and cortex, respectively. The two candidates from the thalamus and the top ten from the cortex were selected for validation. In the thalamus, miR-146a-5p and miR-155-5p levels were upregulated, and in the cortex, miR-375-3p and miR-211-5p levels were upregulated. Analysis of isomiRs of differentially expressed miRNAs identified 3' nucleotide additions that were increased after TBI. Surprisingly, we found fragments originating from 16 and 13 tRNAs in the thalamus and cortex, respectively. We further analyzed two upregulated fragments, 3'tRF-IleAAT and 3'tRF-LysTTT. Increased expression of the full miR-146a profile, and 3'tRF-IleAAT and 3'tRF-LysTTT was associated with a worse behavioral outcome in animals with chronic neuroinflammation. Our results highlight the importance of understanding the regulatory roles of as-yet unknown sncRNAs for developing better strategies to treat TBI and neuroinflammation.

SUBMITTER: Puhakka N

PROVIDER: S-EPMC8773447 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Characterization of circulating transfer RNA-derived RNA fragments in cattle.

Project description:The objective was to characterize naturally occurring circulating transfer RNA-derived RNA fragments (tRFs) in cattle. Serum from eight clinically normal adult dairy cows was collected, and small non-coding RNAs were extracted immediately after collection and sequenced by Illumina MiSeq. Sequences aligned to transfer RNA (tRNA) genes or their flanking sequences were characterized. Sequences aligned to the beginning of 5' end of the mature tRNA were classified as tRF5; those aligned to the 3' end of mature tRNA were classified as tRF3; and those aligned to the beginning of the 3' end flanking sequences were classified as tRF1. There were 3,190,962 sequences that mapped to transfer RNA and small non-coding RNAs in the bovine genome. Of these, 2,323,520 were identified as tRF5s, 562 were tRF3s, and 81 were tRF1s. There were 866,799 sequences identified as other small non-coding RNAs (microRNA, rRNA, snoRNA, etc.) and were excluded from the study. The tRF5s ranged from 28 to 40 nucleotides; and 98.7% ranged from 30 to 34 nucleotides in length. The tRFs with the greatest number of sequences were derived from tRNA of histidine, glutamic acid, lysine, glycine, and valine. There was no association between number of codons for each amino acid and number of tRFs in the samples. The reason for tRF5s being the most abundant can only be explained if these sequences are associated with function within the animal.

| S-EPMC4547532 | biostudies-literature

PtRFdb: a database for plant transfer RNA-derived fragments.

Project description:Transfer RNA-derived fragments (tRFs) represent a novel class of small RNAs (sRNAs) generated through endonucleolytic cleavage of both mature and precursor transfer RNAs (tRNAs). These 14-28 nt length tRFs that have been extensively studied in animal kingdom are to be explored in plants. In this study, we introduce a database of plant tRFs named PtRFdb (www.nipgr.res.in/PtRFdb), for the scientific community. We analyzed a total of 1344 sRNA sequencing datasets of 10 different plant species and identified a total of 5607 unique tRFs (758 tRF-1, 2269 tRF-3 and 2580 tRF-5), represented by 487 765 entries. In PtRFdb, detailed and comprehensive information is available for each tRF entry. Apart from the core information consisting of the tRF type, anticodon, source organism, tissue, sequence and the genomic location; additional information like PubMed identifier (PMID), Sample accession number (GSM), sequence length and frequency relevant to the tRFs may be of high utility to the user. Two different types of search modules (Basic Search and Advanced Search), sequence similarity search (by BLAST) and Browse option with data download facility for each search is provided in this database. We believe that PtRFdb is a unique database of its kind and it will be beneficial in the validation and further characterization of plant tRFs.Database URL: http://www.nipgr.res.in/PtRFdb/.

| S-EPMC6016605 | biostudies-literature

Mycobacterium tuberculosis Infection Drives Mitochondria-Biased Dysregulation of Host Transfer RNA-Derived Fragments.

Project description:BackgroundMycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, causes 10 million infections and 1.5 million deaths per year worldwide. The success of Mtb as a human pathogen is directly related to its ability to suppress host responses, which are critical for clearing intracellular pathogens. Emerging evidence suggests that key response pathways may be regulated by a novel class of small noncoding RNA, called transfer RNA (tRNA)-derived fragments (tRFs). tRFs can complex with Argonaute proteins to target and degrade messenger RNA targets, similarly to micro RNAs, but have thus far been overlooked in the context of bacterial infections.MethodsWe generated a novel miRge2.0-based tRF-analysis tool, tRFcluster, and used it to analyze independently generated and publicly available RNA-sequencing datasets to assess tRF dysregulation in host cells following infection with Mtb and other intracellular bacterial pathogens.ResultsWe found that Mtb and Listeria monocytogenes drive dramatic tRF dysregulation, whereas other bacterial pathogens do not. Interestingly, Mtb infection uniquely increased the expression of mitochondria-derived tRFs rather than genomic-derived tRFs, suggesting an association with mitochondrial damage in Mtb infection.ConclusionstRFs are dysregulated in some, but not all, bacterial infections. Biased dysregulation of mitochondria-derived tRFs in Mtb infection suggests a link between mitochondrial distress and tRF production.

| S-EPMC8161643 | biostudies-literature

IsomiRs and tRNA-derived fragments are associated with metastasis and patient survival in uveal melanoma.

Project description:Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. With over 50% of patients developing metastatic disease, there is an unmet need for improved diagnostic and therapeutic options. Efforts to understand the molecular biology of the disease have revealed several markers that correlate with patient prognosis, including the copy number of chromosome 3, genetic alterations in the BAP1, EIF1AX and SF3B1 genes, and other transcriptional features. Here, we expand upon previous reports by comprehensively characterizing the short RNA-ome in 80 primary UVM tumor samples. In particular, we describe a previously unseen complex network involving numerous regulatory molecules that comprise microRNA (miRNAs), novel UVM-specific miRNA loci, miRNA isoforms (isomiRs), and tRNA-derived fragments (tRFs). Importantly, we show that the abundance profiles of isomiRs and tRFs associate with various molecular phenotypes, metastatic disease, and patient survival. Our findings suggest deep involvement of isomiRs and tRFs in the disease etiology of UVM. We posit that further study and characterization of these novel molecules will improve understanding of the mechanisms underlying UVM, and lead to the development of new diagnostic and therapeutic approaches.

| S-EPMC6928426 | biostudies-literature

Transfer RNA-derived fragments in aging Caenorhabditis elegans originate from abundant homologous gene copies.

Project description:Small RNAs that originate from transfer RNA (tRNA) species, tRNA-derived fragments (tRFs), play diverse biological functions but little is known for their association with aging. Moreover, biochemical aspects of tRNAs limit discovery of functional tRFs by high throughput sequencing. In particular, genes encoding tRNAs exist as multiple copies throughout genome, and mature tRNAs have various modified bases, contributing to ambiguities for RNA sequencing-based analysis of tRFs. Here, we report age-dependent changes of tRFs in Caenorhabditis elegans. We first analyzed published RNA sequencing data by using a new strategy for tRNA-associated sequencing reads. Our current method used unique mature tRNAs as a reference for the sequence alignment, and properly filtered out false positive enrichment for tRFs. Our analysis successfully distinguished de novo mutation sites from differences among homologous copies, and identified potential RNA modification sites. Overall, the majority of tRFs were upregulated during aging and originated from 5'-ends, which we validated by using Northern blot analysis. Importantly, we revealed that the major source of tRFs upregulated during aging was the tRNAs with abundant gene copy numbers. Our analysis suggests that tRFs are useful biomarkers of aging particularly when they originate from abundant homologous gene copies.

| S-EPMC8192933 | biostudies-literature

Transfer RNA Fragments in the Kidney in Hypertension.

Project description:[Figure: see text].

| S-EPMC8370717 | biostudies-literature

Differential Expression Profiles and Function Prediction of Transfer RNA-Derived Fragments in High-Grade Serous Ovarian Cancer.

Project description:BackgroundThe present study is aimed at providing systematic insight into the composition and expression of transfer RNA (tRNA) derivative transcription in high-grade serous ovarian cancer (HGSOC).MethodstRNA derivative expression profiles in three pairs of HGSOC and adjacent normal ovarian tissues were conducted by tRNA-derived small RNA fragment (tRF) and tRNA half (tiRNA) sequencing. The differentially expressed tRFs and tiRNAs between HGSOC and paired adjacent normal samples were screened. The targeted genes of differentially expressed tRFs and tiRNAs were screened. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) of target genes of tRFs and tiRNAs were analyzed.ResultsThere are a total of 20 significantly upregulated and 15 significantly downregulated tRFs and tiRNAs between the cancer group and the paracarcinoma group. The upregulated tRFs and tiRNAs are mucin-type O-glycan biosynthesis, glycosphingolipid biosynthesis, the glucagon signaling pathway, the AMPK signaling pathway, maturity-onset diabetes of the young, glycosphingolipid biosynthesis, the insulin signaling pathway, insulin resistance, leukocyte transendothelial migration, starch, and sucrose metabolism. The downregulated tRFs and tiRNAs are other glycan degradation, vitamin digestion and absorption, fatty acid elongation, and biosynthesis of unsaturated fatty acids.ConclusionsThere are significantly expressed tRFs and tiRNAs in HGSOC tissues, and these may provide potential diagnostic biomarkers and therapeutic targets for HGSOC.

| S-EPMC8028742 | biostudies-literature

Expression profiles of serum transfer RNA-derived fragments and their potential roles in non-small cell lung cancer.

Project description:BackgroundNon-small cell lung cancer (NSCLC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis can significantly improve the prognosis of patients. Transfer RNA (tRNA)-derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the role of tRFs/tRNA halves (tiRNAs) in NSCLC is yet unknown. The present study aimed to investigate unique expression profiles of tRFs/tiRNAs in NSCLC and search novel biomarkers for the diagnosis.MethodsRNA-sequencing was utilized for determining differently expressed tRFs/tiRNAs in serum in NSCLC and healthy controls. Stem-loop quantitative polymerase chain reaction (PCR) was used to confirm the selected tRFs/tiRNAs expressions. Their possible roles in NSCLC were predicted using bioinformatic research.ResultsEleven up-regulated tRFs/tiRNAs and 18 down-regulated tRFs/tiRNAs were determined. Levels of tRF-31-87R8WP9N1EWJ0 and tRF-31-79MP9P9NH57SD were significantly higher in NSCLC serum samples than those of healthy controls; the receiver operating characteristic (ROC) curve suggested that they could serve as new diagnostic biomarkers. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis hinted that tRF-31-87R8WP9N1EWJ0 and tRF-31-79MP9P9NH57SD might influence the development and manifestation of NSCLC.ConclusionsIn NSCLC patients' serum, the tRFs/tiRNAs were abnormally regulated and that tRF-31-87R8WP9N1EWJ0 and tRF-31-79MP9P9NH57SD might be the potential biological markers for NSCLC.

| S-EPMC11322679 | biostudies-literature

Information Transfer and Multifractal Analysis of EEG in Mild Blast-Induced TBI.

Project description:Mild, blast-induced traumatic brain injury (mbTBI) is a common combat brain injury characterized by typically normal neuroimaging findings, with unpredictable future cognitive recovery. Traditional methods of electroencephalography (EEG) analysis (e.g., spectral analysis) have not been successful in detecting the degree of cognitive and functional impairment in mbTBI. We therefore collected resting state EEG (5 minutes, 64 leads) from twelve patients with a history of mbTBI, along with repeat neuropsychological testing (D-KEFS Tower test) to compare two new methods for analyzing EEG (multifractal detrended fluctuation analysis (MF-DFA) and information transfer modeling (ITM)) with spectral analysis. For MF-DFA, we extracted relevant parameters from the resultant multifractal spectrum from all leads and compared with traditional power by frequency band for spectral analysis. For ITM, because the number of parameters from each lead far exceeded the number of subjects, we utilized a reduced set of 10 leads which were compared with spectral analysis. We utilized separate 30 second EEG segments for training and testing statistical models based upon regression tree analysis. ITM and MF-DFA models both generally had improved accuracy at correlating with relevant measures of cognitive performance as compared to spectral analytic models ITM and MF-DFA both merit additional research as analytic tools for EEG and cognition in TBI.

| S-EPMC8051525 | biostudies-literature

Transfer-RNA-Derived Fragments Are Potential Prognostic Factors in Patients with Squamous Cell Carcinoma of the Head and Neck.

Project description:Transfer-RNA-derived fragments (tRFs) are a class of small non-coding RNAs that are functionally different from their parental transfer RNAs (tRNAs). tRFs can regulate gene expression by several mechanisms, and are involved in a variety of pathological processes. Here, we aimed at understanding the composition and abundance of tRFs in squamous cell carcinoma of the head and neck (SCCHN), and evaluated the potential of tRFs as prognostic markers in this cancer type. We obtained tRF expression data from The Cancer Genome Atlas (TCGA) HNSC cohort (523 patients) using MINTbase v2.0, and correlated to available TCGA clinical data. RNA-binding proteins were predicted according to the calculated Position Weight Matrix (PWM) score from the RNA-Binding Protein DataBase (RBPDB). A total of 10,158 tRFs were retrieved and a high diversity in expression levels was seen. Fifteen tRFs were found to be significantly associated with overall survival (Kaplan-Meier survival analysis, log rank test p-value < 0.01). The top prognostic marker, tRF-20-S998LO9D (p < 0.001), was further measured in tumor and tumor-free samples from 16 patients with squamous cell carcinoma of the oral tongue and 12 healthy controls, and was significantly upregulated in tumor compared to matched tumor-free tongue (p < 0.001). Results suggest that tRFs are useful prognostic markers in SCCHN.

| S-EPMC7698123 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data