Howard Hughes Medical Institute, Cambridge, MA, USA.
Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Nature. 2019 Jan;565(7741):606-611. doi: 10.1038/s41586-018-0828-1. Epub 2019 Jan 16.
Spliceosomal introns are ubiquitous non-coding RNAs that are typically destined for rapid debranching and degradation. Here we describe 34 excised introns in Saccharomyces cerevisiae that-despite being rapidly degraded in log-phase growth-accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, which is a key integrator of growth signalling. Introns that become stabilized remain associated with components of the spliceosome and differ from other spliceosomal introns in having a short distance between their lariat branch point and 3' splice site, which is necessary and sufficient for their stabilization. Deletion of these unusual introns is disadvantageous in saturated conditions and causes aberrantly high growth rates in yeast that are chronically challenged with the TORC1 inhibitor rapamycin. The reintroduction of native or engineered stable introns suppresses this aberrant rapamycin response. Thus, excised introns function within the TOR growth-signalling network of S. cerevisiae and, more generally, excised spliceosomal introns can have biological functions.
剪接体内含子是普遍存在的非编码 RNA,通常注定要快速分枝和降解。在这里,我们描述了酿酒酵母中的 34 个剪接体内含子,尽管在对数生长期快速降解,但在饱和生长条件下或其他导致 TORC1 长时间抑制的应激条件下,它们会积累为线性 RNA。TORC1 是生长信号的关键整合因子。稳定的内含子仍然与剪接体的组成部分相关,并且与其他剪接体内含子不同,它们的套索分支点和 3'剪接位点之间的距离很短,这对于它们的稳定是必要和充分的。这些不寻常内含子的缺失在饱和条件下是不利的,并且在酵母中引起异常高的生长速率,酵母长期受到 TORC1 抑制剂 rapamycin 的挑战。这些不寻常内含子的重新引入抑制了这种异常的 rapamycin 反应。因此,剪接体内含子在酿酒酵母的 TOR 生长信号网络中发挥作用,更普遍地说,剪接体内含子可以具有生物学功能。