Daulny Anne, Mejía-Ramírez Eva, Reina Oscar, Rosado-Lugo Jesus, Aguilar-Arnal Lorena, Auer Herbert, Zaratiegui Mikel, Azorin Fernando
Institute of Molecular Biology of Barcelona, CSIC, Baldiri Reixac, 4, 08028 Barcelona, Spain; Institute for Research in Biomedicine, IRB Barcelona, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Institute for Research in Biomedicine, IRB Barcelona, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Biochim Biophys Acta. 2016 Oct;1859(10):1314-21. doi: 10.1016/j.bbagrm.2016.06.009. Epub 2016 Jun 23.
It is well established that eukaryotic genomes are pervasively transcribed producing cryptic unstable transcripts (CUTs). However, the mechanisms regulating pervasive transcription are not well understood. Here, we report that the fission yeast CENP-B homolog Abp1 plays an important role in preventing pervasive transcription. We show that loss of abp1 results in the accumulation of CUTs, which are targeted for degradation by the exosome pathway. These CUTs originate from different types of genomic features, but the highest increase corresponds to Tf2 retrotransposons and rDNA repeats, where they map along the entire elements. In the absence of abp1, increased RNAPII-Ser5P occupancy is observed throughout the Tf2 coding region and, unexpectedly, RNAPII-Ser5P is enriched at rDNA repeats. Loss of abp1 also results in Tf2 derepression and increased nucleolus size. Altogether these results suggest that Abp1 prevents pervasive RNAPII transcription of repetitive DNA elements (i.e., Tf2 and rDNA repeats) from internal cryptic sites.
真核生物基因组广泛转录产生隐蔽性不稳定转录本(CUTs),这一点已得到充分证实。然而,调节广泛转录的机制尚不清楚。在此,我们报道裂殖酵母CENP - B同源物Abp1在防止广泛转录中发挥重要作用。我们发现缺失abp1会导致CUTs积累,这些CUTs会被外泌体途径靶向降解。这些CUTs源自不同类型的基因组特征,但增加最多的对应于Tf2逆转座子和rDNA重复序列,它们沿整个元件定位。在没有abp1的情况下,在整个Tf2编码区域观察到RNAPII - Ser5P占有率增加,并且出乎意料的是,RNAPII - Ser5P在rDNA重复序列处富集。缺失abp1还导致Tf2去抑制和核仁大小增加。总之,这些结果表明Abp1可防止重复DNA元件(即Tf2和rDNA重复序列)从内部隐蔽位点进行广泛的RNAPII转录。