Excised linear introns regulate growth in yeast

Nature. 2019 Jan;565(7741):606-611. doi: 10.1038/s41586-018-0828-1. Epub 2019 Jan 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Genes, Fungal / genetics
  • Genetic Fitness
  • Introns / genetics*
  • Mechanistic Target of Rapamycin Complex 1 / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / genetics
  • Microfilament Proteins / genetics
  • RNA Splice Sites / genetics
  • RNA Stability
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae Proteins / genetics
  • Sirolimus / pharmacology
  • Spliceosomes / metabolism

Substances

  • Act1 protein, S cerevisiae
  • Actins
  • ECM33 protein, S cerevisiae
  • Membrane Glycoproteins
  • Membrane Proteins
  • Microfilament Proteins
  • RNA Splice Sites
  • Saccharomyces cerevisiae Proteins
  • plastin
  • Mechanistic Target of Rapamycin Complex 1
  • Sirolimus