Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
RNA Biol. 2023 Jan;20(1):257-271. doi: 10.1080/15476286.2023.2217392.
The main components of the essential cellular process of eukaryotic ribosome biogenesis are highly conserved from yeast to humans. Among these, the U3 Associated Proteins (UTPs) are a small subunit processome subcomplex that coordinate the first two steps of ribosome biogenesis in transcription and pre-18S processing. While we have identified the human counterparts of most of the yeast Utps, the homologs of yeast Utp9 and Bud21 (Utp16) have remained elusive. In this study, we find that NOL7 is the likely ortholog of Bud21. Previously described as a tumour suppressor through regulation of antiangiogenic transcripts, we now show that NOL7 is required for early pre-rRNA accumulation and pre-18S rRNA processing in human cells. These roles lead to decreased protein synthesis and induction of the nucleolar stress response upon NOL7 depletion. Beyond Bud21's nonessential role in yeast, we establish human NOL7 as an essential UTP that is necessary to maintain both early pre-rRNA levels and processing.
真核生物核糖体生物发生的基本细胞过程的主要成分在从酵母到人之间高度保守。其中,U3 相关蛋白 (UTPs) 是一个小亚基过程体亚复合物,协调转录和前 18S 加工中核糖体生物发生的前两个步骤。虽然我们已经确定了大多数酵母 Utps 的人类对应物,但酵母 Utp9 和 Bud21(Utp16)的同源物仍然难以捉摸。在这项研究中,我们发现 NOL7 可能是 Bud21 的直系同源物。以前通过调节抗血管生成转录本被描述为肿瘤抑制因子,我们现在表明 NOL7 是人细胞中早期前 rRNA 积累和前 18S rRNA 加工所必需的。这些作用导致蛋白质合成减少和核仁应激反应的诱导,当 NOL7 耗尽时。除了 Bud21 在酵母中的非必需作用之外,我们还将人类 NOL7 确立为一种必需的 UTP,它对于维持早期前 rRNA 水平和加工都是必需的。