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| Status |
Public on Apr 20, 2021 |
| Title |
Lack of TRMT2A, a tRNA methyltransferase, induces the generation of tRNA-derived small RNAs due to m5U54 tRNA hypomodification [Array] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Transfer RNA (tRNA) molecules contain a variety of post-transcriptional modifications which are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation, to gene expression control and cellular stress response. Recent evidence show that tsRNAs are also modified, however the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. This modification is catalyzed by the tRNA methyltransferase TRMT2A, but its biological role remains largely unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.
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| Overall design |
Gene expression profiles were generated for HeLa cells transfected with a siCTRL (control condition) and HeLa cells transfected with siTRMT2A samples (tested condition) using customized oligonucleotide microarrays (Agilent Technologies). 3 biological replicates of each condition were analyzed. RNA sample preparation, labeling, hybridization, microarray wash, scanning and feature extraction were performed according to the manufacturer’s protocol: “One-Color Microarray-Based Gene Expression Analysis – Low Input Quick Amp Labeling” version 6.9.1 from Agilent Technologies”. Microarray expression profiles were generated using Agilent’s Feature Extraction software.
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| Contributor(s) |
Pereira M, Soares AR |
| Citation(s) |
33799331 |
| Submission date |
Jan 04, 2021 |
| Last update date |
Apr 20, 2021 |
| Contact name |
Ana Soares |
| E-mail(s) |
ana.r.soares@ua.pt
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| Organization name |
University of Aveiro
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| Street address |
Campus de Santiago
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| City |
Aveiro |
| ZIP/Postal code |
3810 |
| Country |
Portugal |
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| Platforms (1) |
| GPL21185 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Probe Name Version] |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE164406 |
Lack of TRMT2A, a tRNA methyltransferase, induces the generation of tRNA-derived small RNAs due to m5U54 tRNA hypomodification |
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| Relations |
| BioProject |
PRJNA689411 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164168_TRMT2A_complete.xls.gz |
39.5 Mb |
(ftp)(http) |
XLS |
| Processed data included within Sample table |
| Processed data are available on Series record |
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