Altered rRNA processing disrupts nuclear RNA homeostasis via competition for the poly(A)-binding protein Nab2.
Altered rRNA processing disrupts nuclear RNA homeostasis via competition for the poly(A)-binding protein Nab2.
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DOI：
10.1093/nar/gkaa964
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发表时间：
2020-11-18
影响因子：
14.9
通讯作者：
Montpetit B
中科院分区：
文献类型：
--
作者：
Aguilar LC;Paul B;Reiter T;Gendron L;Arul Nambi Rajan A;Montpetit R;Trahan C;Pechmann S;Oeffinger M;Montpetit B
RNA结合蛋白（RBP）是RNA代谢的关键介质。尽管一些RBP表现出狭窄的转录物特异性，但其他RBP在编码和非编码RNA中广泛发挥作用。在这里，在酿酒酵母中，我们证明了RBP可用性的变化所造成的破坏不同的细胞过程中促进一个共同的全球性的崩溃，RNA代谢和核RNA稳态。我们的数据表明，稳定异常的核糖体RNA（rRNA）前体在enp 1 -1突变体的原因表型相似的RNA外泌体突变体由于核仁螯合的聚（A）结合蛋白（PABP）Nab 2。核PABP可用性降低伴随着RNA代谢的全基因组变化，包括普遍的转录水平增加和snoRNA加工缺陷。这些表型通过PABP的过表达、rDNA转录的抑制或TRAMP活性的改变而减轻。我们的研究结果强调了细胞需要保持多聚（A）-RNA水平与PABP和其他RBP在核质和核仁RNA过程中具有可变底物特异性的平衡。
RNA-binding proteins (RBPs) are key mediators of RNA metabolism. Whereas some RBPs exhibit narrow transcript specificity, others function broadly across both coding and non-coding RNAs. Here, in Saccharomyces cerevisiae, we demonstrate that changes in RBP availability caused by disruptions to distinct cellular processes promote a common global breakdown in RNA metabolism and nuclear RNA homeostasis. Our data shows that stabilization of aberrant ribosomal RNA (rRNA) precursors in an enp1-1 mutant causes phenotypes similar to RNA exosome mutants due to nucleolar sequestration of the poly(A)-binding protein (PABP) Nab2. Decreased nuclear PABP availability is accompanied by genome-wide changes in RNA metabolism, including increased pervasive transcripts levels and snoRNA processing defects. These phenotypes are mitigated by overexpression of PABPs, inhibition of rDNA transcription, or alterations in TRAMP activity. Our results highlight the need for cells to maintain poly(A)-RNA levels in balance with PABPs and other RBPs with mutable substrate specificity across nucleoplasmic and nucleolar RNA processes.
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