Stress-induced lncRNAs evade nuclear degradation and enter the translational machinery

Genes Cells. 2013 May;18(5):353-68. doi: 10.1111/gtc.12042. Epub 2013 Mar 12.

Abstract

Long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression. In fission yeast, glucose starvation triggers a transcriptional cascade of polyadenylated lncRNAs in the upstream region of the fructose-1,6-bisphosphatase gene (fbp1(+) ), which is correlated with stepwise chromatin remodeling and necessary for the massive induction of fbp1(+) mRNA. Here, we show that these novel metabolic stress-induced lncRNAs (mlonRNAs) are 5'-capped, less stable than fbp1(+) mRNA and sensitive to a certain extent to the nuclear exosome cofactor Rrp6. However, most mlonRNAs seem to escape nuclear degradation and are exported to the cytoplasm, where they localize to polysomes precisely during glucose starvation-induced global translation inhibition. It is likely that ribosomes tend to accumulate in the upstream region of mlonRNAs. Although mlonRNAs contain an unusual amount of upstream AUGs (uAUGs) and small open reading frames (uORFs), they escape Upf1-mediated targeting to the non-sense-mediated decay (NMD) pathway. The deletion of Upf1 had no effect on mlonRNA stability, but considerably destabilized fbp1(+) mRNA, hinting toward a possible novel role of Upf1. Our findings suggest that the stability of mlonRNAs is distinctly regulated from mRNA and previously described noncoding transcripts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Glucose / pharmacology
  • Half-Life
  • Mutation / genetics
  • Nonsense Mediated mRNA Decay / drug effects
  • Nonsense Mediated mRNA Decay / genetics
  • Nucleic Acid Conformation / drug effects
  • Open Reading Frames / genetics
  • Phenanthrolines / metabolism
  • Polyribosomes / drug effects
  • Polyribosomes / metabolism
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / genetics*
  • RNA Caps / metabolism
  • RNA Stability / drug effects
  • RNA Stability / genetics*
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / genetics*
  • Stress, Physiological / drug effects
  • Stress, Physiological / genetics*

Substances

  • Phenanthrolines
  • RNA Caps
  • RNA, Long Noncoding
  • RNA, Messenger
  • Glucose
  • 1,10-phenanthroline