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Recruitment of Xrn1 to stress-induced genes allows efficient transcription by controlling RNA polymerase II backtracking
RNA Biology ( IF 4.1 ) Pub Date : 2020-12-15 , DOI: 10.1080/15476286.2020.1857521
José García-Martínez 1, 2 , María E Pérez-Martínez 1, 3 , José E Pérez-Ortín 1, 3 , Paula Alepuz 1, 3
Affiliation  

ABSTRACT

A new paradigm has emerged proposing that the crosstalk between nuclear transcription and cytoplasmic mRNA stability keeps robust mRNA levels in cells under steady-state conditions. A key piece in this crosstalk is the highly conserved 5′–3′ RNA exonuclease Xrn1, which degrades most cytoplasmic mRNAs but also associates with nuclear chromatin to activate transcription by not well-understood mechanisms. Here, we investigated the role of Xrn1 in the transcriptional response of Saccharomyces cerevisiae cells to osmotic stress. We show that a lack of Xrn1 results in much lower transcriptional induction of the upregulated genes but in similar high levels of their transcripts because of parallel mRNA stabilization. Unexpectedly, lower transcription in xrn1 occurs with a higher accumulation of RNA polymerase II (RNAPII) at stress-inducible genes, suggesting that this polymerase remains inactive backtracked. Xrn1 seems to be directly implicated in the formation of a competent elongation complex because Xrn1 is recruited to the osmotic stress-upregulated genes in parallel with the RNAPII complex, and both are dependent on the mitogen-activated protein kinase Hog1. Our findings extend the role of Xrn1 in preventing the accumulation of inactive RNAPII at highly induced genes to other situations of rapid and strong transcriptional upregulation.



中文翻译:

将 Xrn1 募集到应激诱导基因通过控制 RNA 聚合酶 II 回溯允许有效转录

摘要

出现了一种新的范式,提出核转录和细胞质 mRNA 稳定性之间的串扰使细胞在稳态条件下保持稳定的 mRNA 水平。这种串扰的一个关键部分是高度保守的 5'-3' RNA 外切核酸酶 Xrn1,它会降解大多数细胞质 mRNA,但也会与核染色质结合,通过尚未充分理解的机制激活转录。在这里,我们研究了 Xrn1 在酿酒酵母细胞对渗透胁迫的转录反应中的作用。我们表明,缺乏 Xrn1 导致上调基因的转录诱导低得多,但由于平行 mRNA 稳定,它们的转录物水平相似。出乎意料的是,xrn1中的转录较低发生在应激诱导基因处的 RNA 聚合酶 II (RNAPII) 积累较高,这表明该聚合酶仍然处于非活性回溯状态。Xrn1 似乎直接参与了有能力的延伸复合物的形成,因为 Xrn1 与 RNAPII 复合物同时被招募到渗透应力上调的基因中,并且两者都依赖于丝裂原活化蛋白激酶 Hog1。我们的研究结果将 Xrn1 在防止高度诱导基因处非活性 RNAPII 积累中的作用扩展到其他快速和强转录上调的情况。

更新日期:2020-12-15
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