RNA polymerase I mutant affects ribosomal RNA processing and ribosomal DNA stability.

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-07-24 DOI:10.1080/15476286.2024.2381910
Christophe Normand, Christophe Dez, Lise Dauban, Sophie Queille, Sarah Danché, Sarra Abderrahmane, Frederic Beckouet, Olivier Gadal
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引用次数: 0

Abstract

Transcription is a major contributor to genomic instability. The ribosomal RNA (rDNA) gene locus consists of a head-to-tail repeat of the most actively transcribed genes in the genome. RNA polymerase I (RNAPI) is responsible for massive rRNA production, and nascent rRNA is co-transcriptionally assembled with early assembly factors in the yeast nucleolus. In Saccharomyces cerevisiae, a mutant form of RNAPI bearing a fusion of the transcription factor Rrn3 with RNAPI subunit Rpa43 (CARA-RNAPI) has been described previously. Here, we show that the CARA-RNAPI allele results in a novel type of rRNA processing defect, associated with rDNA genomic instability. A fraction of the 35S rRNA produced in CARA-RNAPI mutant escapes processing steps and accumulates. This accumulation is increased in mutants affecting exonucleolytic activities of the exosome complex. CARA-RNAPI is synthetic lethal with monopolin mutants that are known to affect the rDNA condensation. CARA-RNAPI strongly impacts rDNA organization and increases rDNA copy number variation. Reduced rDNA copy number suppresses lethality, suggesting that the chromosome segregation defect is caused by genomic rDNA instability. We conclude that a constitutive association of Rrn3 with transcribing RNAPI results in the accumulation of rRNAs that escape normal processing, impacting rDNA organization and affecting rDNA stability.

RNA 聚合酶 I 突变体影响核糖体 RNA 处理和核糖体 DNA 的稳定性。
转录是导致基因组不稳定的主要因素。核糖体 RNA(rDNA)基因座由基因组中转录最活跃的基因头尾重复组成。RNA 聚合酶 I(RNAPI)负责大量产生 rRNA,新生 rRNA 与酵母核仁中的早期组装因子共同转录组装。在酿酒酵母(Saccharomyces cerevisiae)中,转录因子 Rrn3 与 RNAPI 亚基 Rpa43(CARA-RNAPI)融合的 RNAPI 突变体已经被描述过。在这里,我们发现 CARA-RNAPI 等位基因会导致一种新型 rRNA 处理缺陷,并与 rDNA 基因组不稳定性有关。在 CARA-RNAPI 突变体中产生的 35S rRNA 有一部分逃脱了加工步骤并积累起来。在影响外泌体复合体外核酸分解活性的突变体中,这种积累会增加。CARA-RNAPI 与已知会影响 rDNA 缩合的垄断蛋白突变体合成致死。CARA-RNAPI 会强烈影响 rDNA 的组织,并增加 rDNA 的拷贝数变化。rDNA 拷贝数的减少抑制了致死率,这表明染色体分离缺陷是由基因组 rDNA 不稳定性引起的。我们的结论是,Rrn3与转录RNAPI的组成性结合导致了rRNA的积累,这些rRNA逃避了正常的处理,影响了rDNA的组织并影响了rDNA的稳定性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
RNA Biology
RNA Biology 生物-生化与分子生物学
CiteScore
8.60
自引率
0.00%
发文量
82
审稿时长
1 months
期刊介绍: RNA has played a central role in all cellular processes since the beginning of life: decoding the genome, regulating gene expression, mediating molecular interactions, catalyzing chemical reactions. RNA Biology, as a leading journal in the field, provides a platform for presenting and discussing cutting-edge RNA research. RNA Biology brings together a multidisciplinary community of scientists working in the areas of: Transcription and splicing Post-transcriptional regulation of gene expression Non-coding RNAs RNA localization Translation and catalysis by RNA Structural biology Bioinformatics RNA in disease and therapy
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