The University of Edinburgh, Wellcome Trust Centre for Cell Biology, Michael Swann Building, Kings Buildings, Edinburgh EH9 3JR, UK.
The University of Edinburgh, Wellcome Trust Centre for Cell Biology, Michael Swann Building, Kings Buildings, Edinburgh EH9 3JR, UK.
Cell. 2013 Aug 29;154(5):996-1009. doi: 10.1016/j.cell.2013.07.047.
Eukaryotic genomes generate a heterogeneous ensemble of mRNAs and long noncoding RNAs (lncRNAs). LncRNAs and mRNAs are both transcribed by Pol II and acquire 5' caps and poly(A) tails, but only mRNAs are translated into proteins. To address how these classes are distinguished, we identified the transcriptome-wide targets of 13 RNA processing, export, and turnover factors in budding yeast. Comparing the maturation pathways of mRNAs and lncRNAs revealed that transcript fate is largely determined during 3' end formation. Most lncRNAs are targeted for nuclear RNA surveillance, but a subset with 3' cleavage and polyadenylation features resembling the mRNA consensus can be exported to the cytoplasm. The Hrp1 and Nab2 proteins act at this decision point, with dual roles in mRNA cleavage/polyadenylation and lncRNA surveillance. Our data also reveal the dynamic and heterogeneous nature of mRNA maturation, and highlight a subset of "lncRNA-like" mRNAs regulated by the nuclear surveillance machinery.
真核基因组产生了一组不均一的 mRNA 和长非编码 RNA (lncRNA)。lncRNA 和 mRNA 均由 Pol II 转录,并获得 5' 帽和 poly(A)尾,但只有 mRNA 被翻译成蛋白质。为了解决这些类别是如何区分的,我们鉴定了在芽殖酵母中 13 种 RNA 加工、输出和周转因子的全转录组靶标。比较 mRNA 和 lncRNA 的成熟途径表明,转录命运在很大程度上是在 3' 端形成过程中决定的。大多数 lncRNA 被靶向核 RNA 监控,但具有类似于 mRNA 共识的 3' 切割和聚腺苷酸化特征的亚组可以被输出到细胞质。Hrp1 和 Nab2 蛋白在这个决策点起作用,在 mRNA 切割/多聚腺苷酸化和 lncRNA 监控中具有双重作用。我们的数据还揭示了 mRNA 成熟的动态和异质性,并强调了受核监控机制调控的“lncRNA 样”mRNA 的一个亚组。