Journal
DEVELOPMENT
Volume 149, Issue 17, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.200342
Keywords
Aars1; Nrf2; UPR; Perk; Neuronal apoptosis; Zebrafish
Categories
Funding
- National Key Research and Development Program of China
- National Natural Science Foundation of China
- [2019YFA802703]
- [31822033]
- [31771623]
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tRNA synthetase deficiency leads to unfolded protein responses in neuronal disorders. This study identified a mutant zebrafish allele that showed increased neuronal apoptosis and compromised neurogenesis. The aberration in gene expression resulted in protein overloading and activated Perk.
tRNA synthetase deficiency leads to unfolded protein responses in neuronal disorders; however, its function in embryonic neurogenesis remains unclear. This study identified an aars1cq71/cq71 mutant zebrafish allele that showed increased neuronal apoptosis and compromised neurogenesis. aars1 transcripts were highly expressed in primary neural progenitor cells, and their aberration resulted in protein overloading and activated Perk. nfe2l2b, a paralog of mammalian Nfe2l2, which encodes Nrf2, is a pivotal executor of Perk signaling that regulates neuronal phenotypes in aars1cq71/cq71 mutants. Interference of nfe2l2b in nfe2l2b Delta 1/Delta 1 mutants did not affect global larval development. However, aars1cq71/cq71;nfe2l2b Delta 1/Delta 1 mutant embryos exhibited increased neuronal cell survival and neurogenesis compared with their aars1cq71/cq71 siblings. nfe2l2b was harnessed by Perk at two levels. Its transcript was regulated by Chop, an implementer of Perk. It was also phosphorylated by Perk. Both pathways synergistically assured the nuclear functions of nfe2l2b to control cell survival by targeting p53. Our study extends the understanding of tRNA synthetase in neurogenesis and implies that Nrf2 is a cue to mitigate neurodegenerative pathogenesis.
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