2. Academic Validation
  3. Ribosome biogenesis factor Tsr3 is the aminocarboxypropyl transferase responsible for 18S rRNA hypermodification in yeast and humans

Ribosome biogenesis factor Tsr3 is the aminocarboxypropyl transferase responsible for 18S rRNA hypermodification in yeast and humans

  • Nucleic Acids Res. 2016 May 19;44(9):4304-16. doi: 10.1093/nar/gkw244.
Britta Meyer 1,  Jan Philip Wurm 2,  Sunny Sharma 3,  Carina Immer 2,  Denys Pogoryelov 4,  Peter Kötter 1,  Denis L J Lafontaine 3,  Jens Wöhnert 5,  Karl-Dieter Entian 6
Affiliations

Affiliations

  • 1 Institute for Molecular Biosciences, Goethe University, Frankfurt/M, Germany.
  • 2 Institute for Molecular Biosciences, Goethe University, Frankfurt/M, Germany Center of Biomolecular Magnetic Resonance, Goethe University, Frankfurt/M, Germany.
  • 3 RNA Molecular Biology & Center for Microscopy and Molecular Imaging, Fonds National de la Recherche Scientifique (F.R.S./FNRS), Université Libre de Bruxelles (ULB).
  • 4 Institute of Biochemistry, Goethe University, Frankfurt/M, Germany.
  • 5 Institute for Molecular Biosciences, Goethe University, Frankfurt/M, Germany Center of Biomolecular Magnetic Resonance, Goethe University, Frankfurt/M, Germany woehnert@bio.uni-frankfurt.de.
  • 6 Institute for Molecular Biosciences, Goethe University, Frankfurt/M, Germany entian@bio.uni-frankfurt.de.
PMID: 27084949 DOI: 10.1093/nar/gkw244
Abstract

The chemically most complex modification in eukaryotic rRNA is the conserved hypermodified nucleotide N1-methyl-N3-aminocarboxypropyl-pseudouridine (m(1)acp(3)Ψ) located next to the P-site tRNA on the small subunit 18S rRNA. While S-adenosylmethionine was identified as the source of the aminocarboxypropyl (acp) group more than 40 years ago the Enzyme catalyzing the acp transfer remained elusive. Here we identify the cytoplasmic ribosome biogenesis protein Tsr3 as the responsible Enzyme in yeast and human cells. In functionally impaired Tsr3-mutants, a reduced level of acp modification directly correlates with increased 20S pre-rRNA accumulation. The crystal structure of archaeal Tsr3 homologs revealed the same fold as in SPOUT-class RNA-methyltransferases but a distinct SAM binding mode. This unique SAM binding mode explains why Tsr3 transfers the acp and not the methyl group of SAM to its substrate. Structurally, Tsr3 therefore represents a novel class of acp transferase Enzymes.

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