tRNA Maturation Defects Lead to Inhibition of rRNA Processing via Synthesis of pppGpp

Mol Cell. 2019 Jun 20;74(6):1227-1238.e3. doi: 10.1016/j.molcel.2019.03.030. Epub 2019 Apr 16.

Abstract

rRNAs and tRNAs universally require processing from longer primary transcripts to become functional for translation. Here, we describe an unsuspected link between tRNA maturation and the 3' processing of 16S rRNA, a key step in preparing the small ribosomal subunit for interaction with the Shine-Dalgarno sequence in prokaryotic translation initiation. We show that an accumulation of either 5' or 3' immature tRNAs triggers RelA-dependent production of the stringent response alarmone (p)ppGpp in the Gram-positive model organism Bacillus subtilis. The accumulation of (p)ppGpp and accompanying decrease in GTP levels specifically inhibit 16S rRNA 3' maturation. We suggest that cells can exploit this mechanism to sense potential slowdowns in tRNA maturation and adjust rRNA processing accordingly to maintain the appropriate functional balance between these two major components of the translation apparatus.

Keywords: RNA maturation; ppGpp; rRNA; ribosome biogenesis; stringent response; tRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / genetics*
  • Bacillus subtilis / metabolism
  • Base Sequence
  • Gene Expression Regulation, Bacterial*
  • Guanosine Pentaphosphate / biosynthesis*
  • Guanosine Pentaphosphate / genetics
  • Guanosine Triphosphate / metabolism
  • Ligases / genetics
  • Ligases / metabolism
  • Nucleic Acid Conformation
  • Peptide Chain Initiation, Translational*
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / genetics*
  • RNA, Ribosomal, 16S / metabolism
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism
  • Ribosome Subunits, Large, Bacterial / genetics
  • Ribosome Subunits, Large, Bacterial / metabolism
  • Ribosome Subunits, Small, Bacterial / genetics
  • Ribosome Subunits, Small, Bacterial / metabolism

Substances

  • RNA, Ribosomal, 16S
  • Guanosine Pentaphosphate
  • Guanosine Triphosphate
  • RNA, Transfer
  • Ligases
  • guanosine 3',5'-polyphosphate synthetases