Pbp1 和热量限制通过抑制 RNA-DNA 杂交在维持基因组和寿命方面的作用。
Roles for Pbp1 and caloric restriction in genome and lifespan maintenance via suppression of RNA-DNA hybrids.
机构信息
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
出版信息
Dev Cell. 2014 Jul 28;30(2):177-91. doi: 10.1016/j.devcel.2014.05.013.
Intergenic transcription within repetitive loci such as the ribosomal DNA (rDNA) repeats of yeast commonly triggers aberrant recombination. Major mechanisms suppressing aberrant rDNA recombination rely on chromatin silencing or RNAPII repression at intergenic spacers within the repeats. We find ancient processes operating at rDNA intergenic spacers and other loci to maintain genome stability via repression of RNA-DNA hybrids. The yeast Ataxin-2 protein Pbp1 binds noncoding RNA, suppresses RNA-DNA hybrids, and prevents aberrant rDNA recombination. Repression of RNA-DNA hybrids in Pbp1-deficient cells through RNaseH overexpression, deletion of the G4DNA-stabilizing Stm1, or caloric restriction operating via RNaseH/Pif1 restores rDNA stability. Pbp1 also limits hybrids at non-rDNA G4DNA loci including telomeres. Moreover, cells lacking Pbp1 have a short replicative lifespan that is extended upon hybrid suppression. Thus, we find roles for Pbp1 in genome maintenance and reveal that caloric restriction counteracts Pbp1 deficiencies by engaging RNaseH and Pif1.
基因间转录在重复序列中很常见，如酵母的核糖体 DNA(rDNA)重复序列，通常会引发异常重组。抑制异常 rDNA 重组的主要机制依赖于重复序列中基因间间隔区的染色质沉默或 RNAPII 抑制。我们发现，古老的过程在 rDNA 基因间间隔区和其他基因座上发挥作用，通过抑制 RNA-DNA 杂交来维持基因组稳定性。酵母 Ataxin-2 蛋白 Pbp1 结合非编码 RNA，抑制 RNA-DNA 杂交，并防止异常 rDNA 重组。通过 RNaseH 过表达、删除 G4DNA 稳定蛋白 Stm1 或通过 RNaseH/Pif1 作用的热量限制来抑制 Pbp1 缺陷细胞中的 RNA-DNA 杂交，恢复 rDNA 稳定性。Pbp1 还限制包括端粒在内的非 rDNA G4DNA 基因座中的杂交。此外，缺乏 Pbp1 的细胞具有较短的复制寿命，通过抑制杂交可以延长。因此，我们发现 Pbp1 在基因组维护中的作用，并揭示热量限制通过结合 RNaseH 和 Pif1 来对抗 Pbp1 的缺乏。
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