Chen Luxi, Xu Wei, Liu Kunpeng, Jiang Zheng, Han Yang, Jin Hongbin, Zhang Lin, Shen Weimin, Jia Shunji, Sun Qianwen, Meng Anming
Laboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Sci Adv. 2021 Nov 19;7(47):eabh0494. doi: 10.1126/sciadv.abh0494.
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 and 5′tRFl function to promote transcription of corresponding tRNA genes and are essential for vertebrate early embryogenesis. During zebrafish embryogenesis, dynamics of 5′tRFl and 5′tRFl levels correlates with that of tRNA and tRNA levels. Morpholino-mediated knockdown of 5′tRFl or 5′tRFl down-regulates tRNA or tRNA 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.
5′端tRNA片段（5′tRFls）是源自成熟tRNA 5′端一半的小转运RNA（tRNA）片段。然而，5′tRFls是否能反馈调节tRNA生物合成尚不清楚。在此，我们表明5′tRFl和5′tRFl的功能是促进相应tRNA基因的转录，并且对脊椎动物早期胚胎发育至关重要。在斑马鱼胚胎发育过程中，5′tRFl和5′tRFl水平的动态变化与tRNA和tRNA水平的动态变化相关。吗啉代介导的5′tRFl或5′tRFl敲低分别下调tRNA或tRNA水平，并导致胚胎致死，通过共注射正确重折叠的相应tRNA可有效挽救这种致死现象。在斑马鱼胚胎中，tRNA:DNA和5′tRFl:DNA杂交体通常存在于tRNA基因的模板链上。从机制上讲，不稳定的5′tRFl:DNA杂交体可能会阻止在同一tRNA基因座上形成转录抑制性稳定tRNA:DNA杂交体，从而促进tRNA基因转录。这一发现的机制可能与其他生理和病理过程有关。
