Guide-independent Pseudouridine synthase

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Function

The alternative to using the RNA-guided mechanism for pseudouridine formation is a guide-independent mechanism acting through stand-alone enzymes. In eukaryotes, these enzymes are called Pus enzymes (Pseudouridine synthases), and they modify uridine by recognizing sequence and/or secondary structural elements of the RNA containing the target uridine.

pseudouridine synthase (PUS) catalyzes the conversion of uridine to tRNA pseudouridine in several types of RNA molecules[1], [2]. tRNAs are well-characterized as targets of these protein-only pseudouridine synthases, but recently have even been found to act on messenger RNAs in a variety of eukaryotic organisms, including humans[3], [4], [5]. In eubacteria PUS are active in the ribosomal large subunit Ribosomal large subunit pseudouridine synthase and in the ribosomal small subunit Ribosomal small subunit pseudouridine synthase.

Ribosomal large subunit pseudouridine synthases:

  • RluA is responsible for synthesis of pseudouridine from uracil in positions 746 in 23S ribosomal RNA and in the anticodon loop of tRNAPhe, tRNACys and tRNALeu[6].
  • RluB is responsible for synthesis of pseudouridine from uracil in position 2605 in 23S ribosomal RNA[7].
  • RluC is responsible for synthesis of pseudouridine from uracil in positions 955, 2504 and 2580 in 23S ribosomal RNA[8].
  • RluD is responsible for synthesis of pseudouridine from uracil in positions 1911, 1915 and 1917 in 23S ribosomal RNA[9].
  • RluE is responsible for synthesis of pseudouridine from uracil in position 2457 in 23S ribosomal RNA[10].
  • RluF is responsible for synthesis of pseudouridine from uracil in position 2604 in 23S ribosomal RNA[11].

Ribosomal small subunit pseudouridine synthase RsuA is responsible for synthesis of pseudouridine from uracil in positions 516 in 16S ribosomal RNA[12].

Structural highlights

The conversion of uridine to pseudouridine causes conformational change of PUS[13]. (1ze2).

tRNA pseudouridine synthase complex with RNA and pseudouridine monophosphate 1ze2

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3D Structures of guide-independent pseudouridine synthase3D Structures of guide-independent pseudouridine synthase

Updated on 13-November-2018

ReferencesReferences

  1. ↑ Pan H, Agarwalla S, Moustakas DT, Finer-Moore J, Stroud RM. Structure of tRNA pseudouridine synthase TruB and its RNA complex: RNA recognition through a combination of rigid docking and induced fit. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12648-53. Epub 2003 Oct 17. PMID:14566049 doi:10.1073/pnas.2135585100
  2. ↑ Rintala-Dempsey AC, Kothe U. Eukaryotic stand-alone pseudouridine synthases - RNA modifying enzymes and emerging regulators of gene expression? RNA Biol. 2017 Sep 2;14(9):1185-1196. doi: 10.1080/15476286.2016.1276150. Epub, 2017 Jan 3. PMID:28045575 doi:http://dx.doi.org/10.1080/15476286.2016.1276150
  3. ↑ Carlile TM, Rojas-Duran MF, Zinshteyn B, Shin H, Bartoli KM, Gilbert WV. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature. 2014 Nov 6;515(7525):143-6. doi: 10.1038/nature13802. Epub 2014 Sep 5. PMID:25192136 doi:http://dx.doi.org/10.1038/nature13802
  4. ↑ Zhao BS, He C. Pseudouridine in a new era of RNA modifications. Cell Res. 2015 Feb;25(2):153-4. doi: 10.1038/cr.2014.143. Epub 2014 Nov 4. PMID:25367125 doi:http://dx.doi.org/10.1038/cr.2014.143
  5. ↑ Adachi H, De Zoysa MD, Yu YT. Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs. Biochim Biophys Acta Gene Regul Mech. 2018 Nov 8. pii: S1874-9399(18)30194-9., doi: 10.1016/j.bbagrm.2018.11.002. PMID:30414851 doi:http://dx.doi.org/10.1016/j.bbagrm.2018.11.002
  6. ↑ Hoang C, Chen J, Vizthum CA, Kandel JM, Hamilton CS, Mueller EG, Ferre-D'Amare AR. Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure. Mol Cell. 2006 Nov 17;24(4):535-45. PMID:17188032 doi:10.1016/j.molcel.2006.09.017
  7. ↑ Czudnochowski N, Ashley GW, Santi DV, Alian A, Finer-Moore J, Stroud RM. The mechanism of pseudouridine synthases from a covalent complex with RNA, and alternate specificity for U2605 versus U2604 between close homologs. Nucleic Acids Res. 2013 Nov 7. PMID:24214967 doi:http://dx.doi.org/10.1093/nar/gkt1050
  8. ↑ Conrad J, Sun D, Englund N, Ofengand J. The rluC gene of Escherichia coli codes for a pseudouridine synthase that is solely responsible for synthesis of pseudouridine at positions 955, 2504, and 2580 in 23 S ribosomal RNA. J Biol Chem. 1998 Jul 17;273(29):18562-6. PMID:9660827
  9. ↑ Gutgsell NS, Deutscher MP, Ofengand J. The pseudouridine synthase RluD is required for normal ribosome assembly and function in Escherichia coli. RNA. 2005 Jul;11(7):1141-52. doi: 10.1261/rna.2550105. Epub 2005 May 31. PMID:15928344 doi:http://dx.doi.org/10.1261/rna.2550105
  10. ↑ Pan H, Ho JD, Stroud RM, Finer-Moore J. The crystal structure of E. coli rRNA pseudouridine synthase RluE. J Mol Biol. 2007 Apr 13;367(5):1459-70. Epub 2007 Feb 7. PMID:17320904 doi:10.1016/j.jmb.2007.01.084
  11. ↑ Sunita S, Zhenxing H, Swaathi J, Cygler M, Matte A, Sivaraman J. Domain organization and crystal structure of the catalytic domain of E.coli RluF, a pseudouridine synthase that acts on 23S rRNA. J Mol Biol. 2006 Jun 16;359(4):998-1009. Epub 2006 Apr 25. PMID:16712869 doi:10.1016/j.jmb.2006.04.019
  12. ↑ Sivaraman J, Sauve V, Larocque R, Stura EA, Schrag JD, Cygler M, Matte A. Structure of the 16S rRNA pseudouridine synthase RsuA bound to uracil and UMP. Nat Struct Biol. 2002 May;9(5):353-8. PMID:11953756 doi:10.1038/nsb788
  13. ↑ Phannachet K, Huang RH. Conformational change of pseudouridine 55 synthase upon its association with RNA substrate. Nucleic Acids Res. 2004 Feb 27;32(4):1422-9. Print 2004. PMID:14990747 doi:10.1093/nar/gkh287

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