PUF-8, a C. elegans ortholog of the RNA-binding proteins PUM1 and PUM2, is required for robustness of the cell death fate.

PUF-8, a C. elegans ortholog of the RNA-binding proteins PUM1 and PUM2, is required for robustness of the cell death fate.
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PUF-8是RNA结合蛋白PUM1和PUM2的秀丽隐杆线虫直系同源物,是细胞死亡命运的鲁棒性所必需的。

DOI:
10.1242/dev.201167
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发表时间:
2023-10-01
期刊:
Development (Cambridge, England)
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在C.在线虫的发育过程中,产生了1090个体细胞,其中959个存活,131个死亡,许多是通过细胞凋亡。我们提出的证据表明,PUF-8,一个C。哺乳动物RNA-结合蛋白G11和G12的直向同源物,是这种“生存和死亡”模式的稳健性所必需的。我们发现,PUF-8可以防止正常存活的细胞的不适当死亡,并且我们提出的证据表明,PUF-8的这种抗凋亡活性取决于PUF-8与ced-3相互作用的能力(C.半胱天冬酶的elegans直系同源物)mRNA,从而抑制促凋亡ced-3基因的活性。PUF-8还促进程序性死亡的细胞的死亡,并且我们提出PUF-8的这种促凋亡活性可能取决于PUF-8抑制抗凋亡ced-9基因表达的能力(a C. elegans的直系同源物)。我们的研究结果表明,细胞凋亡途径中基因表达的随机差异可以破坏C.这种差异在线虫发育中起重要作用,并且PUF-8在转录后水平起作用以消除这些差异,从而确保适当的细胞数量稳态。总结:RNA结合蛋白PUF-8是C. elegans发育
During C. elegans development, 1090 somatic cells are generated, of which 959 survive and 131 die, many through apoptosis. We present evidence that PUF-8, a C. elegans ortholog of the mammalian RNA-binding proteins PUM1 and PUM2, is required for the robustness of this ‘survival and death’ pattern. We found that PUF-8 prevents the inappropriate death of cells that normally survive, and we present evidence that this anti-apoptotic activity of PUF-8 is dependent on the ability of PUF-8 to interact with ced-3 (a C. elegans ortholog of caspase) mRNA, thereby repressing the activity of the pro-apoptotic ced-3 gene. PUF-8 also promotes the death of cells that are programmed to die, and we propose that this pro-apoptotic activity of PUF-8 may depend on the ability of PUF-8 to repress the expression of the anti-apoptotic ced-9 gene (a C. elegans ortholog of Bcl2). Our results suggest that stochastic differences in the expression of genes within the apoptosis pathway can disrupt the highly reproducible and robust survival and death pattern during C. elegans development, and that PUF-8 acts at the post-transcriptional level to level out these differences, thereby ensuring proper cell number homeostasis. Summary: The RNA-binding protein PUF-8 is required for the highly reproducible and robust pattern of cell survival and cell death during C. elegans development.
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