Wery Maxime, Szachnowski Ugo, Andjus Sara, de Andres-Pablo Alvaro, Morillon Antonin
ncRNA, Epigenetic and Genome Fluidity, Institut Curie, Sorbonne Université, CNRS UMR3244, Paris Cedex, France.
ncRNA, Epigenetic and Genome Fluidity, Institut Curie, PSL University, Sorbonne Université, CNRS UMR3244, Paris Cedex, France.
Front RNA Res. 2023 Aug 7;1:1244554. doi: 10.3389/frnar.2023.1244554.
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.
酵母长链非编码(lnc)RNA的表达受到RNA监测机制的限制,其中包括细胞质5'-3'核酸外切酶Xrn1,它作用于一类保守的lncRNA家族,即XUTs,这些XUTs主要与蛋白质编码基因呈反义关系。然而,参与这些转录本降解的辅助因子及其潜在的分子机制在很大程度上仍不清楚。在这里,我们表明两种RNA解旋酶Dbp2和Mtr4是XUTs表达的全局调节因子。通过RNA测序,我们发现它们中的大多数在Dbp2失活或Mtr4缺失时会积累。细胞质RNA解旋酶Ecm32、Ski2、Slh1、Dbp1和Dhh1的突变体并没有重现XUTs的这种全局稳定现象,这表明XUTs的降解是由Dbp2和Mtr4特异性控制的。值得注意的是,Dbp2和Mtr4对XUTs的影响与其相对于配对正义mRNA的构型无关。最后,我们表明Dbp2对XUTs的影响取决于其细胞质定位。总体而言,我们的数据表明Dbp2和Mtr4是lncRNA表达的全局调节因子,并与RNA降解机制一起共同塑造非编码转录组。