Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Strang Laboratory of Apoptosis and Cancer Biology, The Rockefeller University, New York, NY 10065, USA.
Cell Rep. 2017 Oct 17;21(3):758-772. doi: 10.1016/j.celrep.2017.09.067.
Non-coding RNA biogenesis in higher eukaryotes has not been fully characterized. Here, we studied the Drosophila melanogaster Rexo5 (CG8368) protein, a metazoan-specific member of the DEDDh 3'-5' single-stranded RNA exonucleases, by genetic, biochemical, and RNA-sequencing approaches. Rexo5 is required for small nucleolar RNA (snoRNA) and rRNA biogenesis and is essential in D. melanogaster. Loss-of-function mutants accumulate improperly 3' end-trimmed 28S rRNA, 5S rRNA, and snoRNA precursors in vivo. Rexo5 is ubiquitously expressed at low levels in somatic metazoan cells but extremely elevated in male and female germ cells. Loss of Rexo5 leads to increased nucleolar size, genomic instability, defective ribosome subunit export, and larval death. Loss of germline expression compromises gonadal growth and meiotic entry during germline development.
高等真核生物中非编码 RNA 的生物发生尚未完全阐明。在这里,我们通过遗传、生化和 RNA 测序方法研究了果蝇 Rexo5(CG8368)蛋白,它是一种真核生物特异性的 DEDDh 3' -5'单链 RNA 外切酶。Rexo5 参与小核仁 RNA(snoRNA)和 rRNA 的生物发生,在果蝇中是必需的。功能丧失突变体在体内积累了未正确 3'端修剪的 28S rRNA、5S rRNA 和 snoRNA 前体。Rexo5 在体细胞真核细胞中低水平广泛表达,但在雄性和雌性生殖细胞中高度表达。Rexo5 的缺失会导致核仁增大、基因组不稳定、核糖体亚基输出缺陷和幼虫死亡。生殖细胞中 Rexo5 的缺失会影响生殖细胞发育过程中的生殖腺生长和减数分裂进入。