The RNA helicases Dbp2 and Mtr4 regulate the expression of Xrn1-sensitive long non-coding RNAs in yeast.

Maxime Wery, Ugo Szachnowski, Sara Andjus, Alvaro de Andres-Pablo, Antonin Morillon
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Abstract

The expression of yeast long non-coding (lnc)RNAs is restricted by RNA surveillance machineries, including the cytoplasmic 5'-3' exonuclease Xrn1 which targets a conserved family of lncRNAs defined as XUTs, and that are mainly antisense to protein-coding genes. However, the co-factors involved in the degradation of these transcripts and the underlying molecular mechanisms remain largely unknown. Here, we show that two RNA helicases, Dbp2 and Mtr4, act as global regulators of XUTs expression. Using RNA-Seq, we found that most of them accumulate upon Dbp2 inactivation or Mtr4 depletion. Mutants of the cytoplasmic RNA helicases Ecm32, Ski2, Slh1, Dbp1, and Dhh1 did not recapitulate this global stabilization of XUTs, suggesting that XUTs decay is specifically controlled by Dbp2 and Mtr4. Notably, Dbp2 and Mtr4 affect XUTs independently of their configuration relative to their paired-sense mRNAs. Finally, we show that the effect of Dbp2 on XUTs depends on a cytoplasmic localization. Overall, our data indicate that Dbp2 and Mtr4 are global regulators of lncRNAs expression and contribute to shape the non-coding transcriptome together with RNA decay machineries.

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RNA解旋酶Dbp2和Mtr4调节酵母中xrn1敏感的长链非编码RNA的表达。
酵母长链非编码(lnc)RNA的表达受到RNA监视机制的限制,包括胞质5'-3'外切酶Xrn1,其靶向被定义为xut的lncrna保守家族,并且主要是蛋白质编码基因的反义。然而,参与这些转录物降解的辅助因子和潜在的分子机制在很大程度上仍然未知。在这里,我们发现两种RNA解旋酶,Dbp2和Mtr4,作为XUTs表达的全局调节因子。使用RNA-Seq,我们发现它们中的大多数在Dbp2失活或Mtr4耗尽时积累。细胞质RNA解旋酶Ecm32、Ski2、Slh1、Dbp1和Dhh1的突变体没有重现xut的这种全局稳定,这表明xut的衰减是由Dbp2和Mtr4特异性控制的。值得注意的是,Dbp2和Mtr4对xut的影响独立于它们相对于成对意义mrna的结构。最后,我们发现Dbp2对xut的影响取决于细胞质定位。总体而言,我们的数据表明,Dbp2和Mtr4是lncRNAs表达的全局调控因子,并与RNA衰变机制一起有助于形成非编码转录组。
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