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.