tRNA-derived fragments (tRFs) are a class of emerging post-transcriptional regulators of gene expression likely binding to the transcripts of target genes. However, only a few tRFs targets have been experimentally validated, making it hard to extrapolate the functions or binding mechanisms of tRFs. The paucity of resources supporting the identification of the targets of tRFs creates a bottleneck in the fast-developing field. We have previously analyzed chimeric reads in crosslinked Argonaute1-RNA complexes to help infer the guide-target pairs and binding mechanisms of multiple tRFs based on experimental data in human HEK293 cells. To efficiently disseminate these results to the research community, we designed a web-based database tatDB (targets of tRFs DataBase) populated with close to 250 000 experimentally determined guide-target pairs with ∼23 000 tRF isoforms. tatDB has a user-friendly interface with flexible query options/filters allowing one to obtain comprehensive information on given tRFs (or targets). Modes of interactions are supported by secondary structures of potential guide-target hybrids and binding motifs, essential for understanding the targeting mechanisms of tRFs. Further, we illustrate the value of the database on an example of hypothesis-building for a tRFs potentially involved in the lifecycle of the SARS-CoV-2 virus. tatDB is freely accessible at https://grigoriev-lab.camden.rutgers.edu/tatdb.
- Award ID(s):
- 1916246
- NSF-PAR ID:
- 10274599
- Date Published:
- Journal Name:
- Nucleic Acids Research
- Volume:
- 49
- Issue:
- D1
- ISSN:
- 0305-1048
- Page Range / eLocation ID:
- D254 to D260
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract tRFtarget 1.0 (http://trftarget.net/) is a platform consolidating both computationally predicted and experimentally validated binding sites between transfer RNA-derived fragments (tRFs) and target genes (or transcripts) across multiple organisms. Here, we introduce a newly released version of tRFtarget 2.0, in which we integrated 6 additional tRF sources, resulting in a comprehensive collection of 2614 high-quality tRF sequences spanning across 9 species, including 1944 Homo sapiens tRFs and one newly incorporated species Rattus norvegicus. We also expanded target genes by including ribosomal RNAs, long non-coding RNAs, and coding genes >50 kb in length. The predicted binding sites have surged up to approximately 6 billion, a 20.5-fold increase than that in tRFtarget 1.0. The manually curated publications relevant to tRF targets have increased to 400 and the gene-level experimental evidence has risen to 232. tRFtarget 2.0 introduces several new features, including a web-based tool that identifies potential binding sites of tRFs in user's own datasets, integration of standardized tRF IDs, and inclusion of external links to contents within the database. Additionally, we enhanced website framework and user interface. With these improvements, tRFtarget 2.0 is more user-friendly, providing researchers a streamlined and comprehensive platform to accelerate their research progress.
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Bradford, Patricia A. (Ed.)
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