5′ Half of specific tRNAs feeds back to promote corresponding tRNA gene transcription in vertebrate embryos

5'tRFls are small transfer RNA (tRNA) fragments derived from 5' half of mature tRNAs. However, it is unknown whether 5'tRFls could feed back to regulate tRNA biogenesis. Here, we show that 5'tRFl(Gly/GCC) and 5'tRFl(Glu/CTC) function to promote transcription of corresponding tRNA genes and are essential for vertebrate early embryogenesis. During zebrafish embryogenesis, dynamics of 5'tRFl(Gly/GCC) and 5'tRFl(Glu/CTC) levels correlates with that of tRNA(Gly/GCC) and tRNA(Glu/CTC) levels. Morpholino-mediated knockdown of 5'tRFl(Gly/GCC) or 5'tRFl(Glu/CTC) down-regulates tRNA(Gly/GCC) or tRNA(Glu/CTC) levels, respectively, and causes embryonic lethality that is efficiently rescued by coinjection of properly refolded corresponding tRNA. In zebrafish embryos, tRNA:DNA and 5'tRFl:DNA hybrids commonly exist on the template strand of tRNA genes. Mechanistically, unstable 5'tRFl:DNA hybrid may prevent the formation of transcriptionally inhibitory stable tRNA:DNA hybrids on the same tRNA loci so as to facilitate tRNA gene transcription. The uncovered mechanism may be implicated in other physiological and pathological processes.

Automated summary

The study demonstrates that 5'tRFls promote transcription of corresponding tRNA genes and are essential for early vertebrate embryogenesis. The levels of 5'tRFls correlate with tRNA levels during zebrafish embryogenesis, and their knockdown leads to embryonic lethality, which can be rescued by restoring the corresponding tRNA levels. Additionally, the presence of tRNA:DNA and 5'tRFl:DNA hybrids on the template strand of tRNA genes in zebrafish embryos may facilitate tRNA gene transcription by preventing the formation of inhibitory stable tRNA:DNA hybrids.