Abstract
5'tiRNAs are small tRNA fragments derived from 5' half of mature tRNAs. However, it remains elusive whether and how 5'tiRNAs regulate embryonic development. Here we show that 5'tiRNAGly/GCC and 5'tiRNAGlu/CTC assist transcription of corresponding tRNA genes in vertebrate embryos. During zebrafish embryogenesis, 5'tiRNAGly/GCC and 5'tiRNAGlu/CTC are abundant and their levels correlate with tRNAGly/GCC and tRNAGlu/CTC levels. Morpholino-mediated knockdown of 5'tiRNAGly/GCC or 5'tiRNAGlu/CTC down-regulates tRNAGly/GCC or tRNAGlu/CTC levels respectively, and causes embryonic lethality that is efficiently rescued by co-injection of the corresponding RNA mimetics. In zebrafish embryos, tRNA:DNA hybrid commonly exist on the template strand of tRNA genes, acting as a transcription brake. On the other hand, 5'tiRNA can competitively bind the same template strand and acts as an anti-brake to prevent tRNA:DNA hybrid formation so as to facilitate tRNA genes transcription. The anti-brake function of 5'tiRNAs is essential to satisfy the increasing demand for more tRNAs during rapid embryonic development.
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