Database Commons

a catalog of worldwide biological databases

We have created tRFdb, the first database of transfer RNA fragments (tRFs), available at http://genome.bioch.virginia.edu/trfdb/. With over 100 small RNA libraries analyzed, the database currently contains the sequences and read counts of the three classes of tRFs for eight species: R. sphaeroides, S. pombe, D. melanogaster, C. elegans, Xenopus, zebra fish, mouse and human, for a total of 12,877 tRFs. The database can be searched by tRF ID or tRF sequence, and the results can be limited by organism. The search results show the genome coordinates and names of the tRNAs the sequence may derive from, and there are links for the sequence of the tRF and parental tRNA, and links for the read counts in all the corresponding small RNA libraries. As a case study for how this database may be used, we have shown that a certain class of tRFs, tRF-1s, is highly upregulated in B-cell malignancies. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

BACKGROUND: tRFs, 14 to 32 nt long single-stranded RNA derived from mature or precursor tRNAs, are a recently discovered class of small RNA that have been found to be present in diverse organisms at read counts comparable to miRNAs. Currently, there is a debate about their biogenesis and function.
RESULTS: This is the first meta-analysis of tRFs. Analysis of more than 50 short RNA libraries has revealed that tRFs are precisely generated fragments present in all domains of life (bacteria to humans), and are not produced by the miRNA biogenesis pathway. Human PAR-CLIP data shows a striking preference for tRF-5s and tRF-3s to associate with AGO1, 3 and 4 rather than AGO2, and analysis of positional T to C mutational frequency indicates these tRFs associate with Argonautes in a manner similar to miRNAs. The reverse complements of canonical seed positions in these sequences match cross-link centered regions, suggesting these tRF-5s and tRF-3s interact with RNAs in the cell. Consistent with these results, human AGO1 CLASH data contains thousands of tRF-5 and tRF-3 reads chimeric with mRNAs.
CONCLUSIONS: tRFs are an abundant class of small RNA present in all domains of life whose biogenesis is distinct from miRNAs. In human HEK293 cells tRFs associate with Argonautes 1, 3 and 4 and not Argonaute 2 which is the main effector protein of miRNA function, but otherwise have very similar properties to miRNAs, indicating tRFs may play a major role in RNA silencing.