Skip to main content
SpringerLink
Log in

An Unusual Recent Expansion of the C-Terminal Domain of RNA Polymerase II in Primate Malaria Parasites Features a Motif Otherwise Found Only in Mammalian Polymerases

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

The tail of the enzyme RNA polymerase II is responsible for integrating the diverse events of gene expression in eukaryotes and is indispensable for life in yeast, fruit flies, and mice. The tail features a C-terminal domain (CTD), which is comprised of tandemly repeated Y1-S2-P3-T4-S5-P6-S7 amino acid heptads that are highly conserved across evolutionary lineages, with all mammalian polymerases featuring 52 identical heptad repeats. However, the composition and function of protozoan CTDs remain less well understood. We find that malaria parasites (genus Plasmodium) display an unprecedented plasticity within the length and composition of their CTDs. The CTD in malaria parasites which infect human and nonhuman primates has expanded compared to closely related species that infect rodents or birds. In addition, this variability extends to different isolates within a single species, such as isolates of the human malaria parasite, Plasmodium falciparum. Our results indicate that expanded CTD heptads in malaria parasites correlates with parasitism of primates and provide the first demonstration of polymorphism of the RNA polymerase II CTD within a single species. The expanded set of CTD heptads feature lysine in the seventh position (Y1-S2-P3-T4-S5-P6-K7), a sequence only seen otherwise in the distal portion of mammalian polymerases. These observations raise new questions for the radiation of malaria parasites into diverse hosts and for the molecular evolution of RNA polymerase II.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CTD:

Carboxy-terminal domain or C-terminal domain

References

  • Allison LA, Moyle M, Shales M, Ingles CJ (1985) Extensive homology among the largest subunits of eukaryotic and prokaryotic RNA polymerases. Cell 42:599–610

    Article  PubMed  CAS  Google Scholar 

  • Aravind L, Iyer LM, Wellems TE, Miller LH (2003) Plasmodium biology: genomic gleanings. Cell 115:771–785

    Article  PubMed  CAS  Google Scholar 

  • Barron-Casella E, Corden JL (1992) Conservation of the mammalian RNA polymerase II largest-subunit C-terminal domain. J Mol Evol 35:405–410

    Article  PubMed  CAS  Google Scholar 

  • Bartolomei MS, Halden NF, Cullen CR, Corden JL (1988) Genetic analysis of the repetitive carboxyl-terminal domain of the largest subunit of mouse RNA polymerase II. Mol Cell Biol 8:330–339

    PubMed  CAS  Google Scholar 

  • Bienkiewicz EA, Moon WA, Woody RW (2000) Conformation of the RNA polymerase II C-terminal domain: circular dichroism of long and short fragments. J Mol Biol 297:119–133

    Article  PubMed  CAS  Google Scholar 

  • Carty SM, Greenleaf AL (2002) Hyperphosphorylated C-terminal repeat domain-associating proteins in the nuclear proteome link transcription to DNA/chromatin modification and RNA processing. Mol Cell Proteomics 1:598–610

    Article  PubMed  CAS  Google Scholar 

  • Chapman AB, Agabian N (1994) Trypanosoma brucei RNA polymerase II is phosphorylated in the absence of carboxyl-terminal domain heptapeptide repeats. J Biol Chem 269:4754–4760

    PubMed  CAS  Google Scholar 

  • Chapman RD, Conrad M, Eick D (2005) Role of the mammalian RNA polymerase II C-terminal domain (CTD) nonconsensus repeats in CTD stability and cell proliferation. Mol Cell Biol 25:7665–7674

    Article  PubMed  CAS  Google Scholar 

  • Chapman RD et al (2007) Transcribing RNA polymerase II is phosphorylated at CTD residue serine-7. Science 318:1780–1782

    Article  PubMed  CAS  Google Scholar 

  • Chapman RD, Heidemann M, Hintermair C, Eick D (2008) Molecular evolution of the RNA polymerase II CTD. Trends Genet 24:289–296

    Article  PubMed  CAS  Google Scholar 

  • Corden JL (1990) Tails of RNA polymerase II. Trends Biochem Sci 15:383–387

    Article  PubMed  CAS  Google Scholar 

  • Corden JL (2007) Transcription: Seven ups the code. Science 318:1735–1736

    Article  PubMed  CAS  Google Scholar 

  • Dacks JB, Marinets A, Ford DW, Cavalier-Smith T, Logsdon JM Jr (2002) Analyses of RNA polymerase II genes from free-living protists: phylogeny, long branch attraction, and the eukaryotic big bang. Mol Biol Evol 19:830–840

    PubMed  CAS  Google Scholar 

  • Egloff S, Murphy S (2008) Cracking the RNA polymerase II CTD code. Trends Genet 24:280–288

    Article  PubMed  CAS  Google Scholar 

  • Egloff S et al (2007) Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene expression. Science 318:1777–1779

    Article  PubMed  CAS  Google Scholar 

  • Giesecke H, Barale JC, Langsley G, Cornelissen AW (1991) The C-terminal domain of RNA polymerase II of the malaria parasite Plasmodium berghei. Biochem Biophys Res Commun 180:1350–1355

    Article  PubMed  CAS  Google Scholar 

  • Guo Z, Stiller JW (2005) Comparative genomics and evolution of proteins associated with RNA polymerase II C-terminal domain. Mol Biol Evol 22:2166–2178

    Article  PubMed  CAS  Google Scholar 

  • Howe KJ (2002) RNA polymerase II conducts a symphony of pre-mRNA processing activities. Biochim Biophys Acta 1577:308–324

    PubMed  CAS  Google Scholar 

  • Iyer LM, Anantharaman V, Wolf MY, Aravind L (2008) Comparative genomics of transcription factors and chromatin proteins in parasitic protists and other eukaryotes. Int J Parasitol 38:1–31

    Article  PubMed  CAS  Google Scholar 

  • Li WB, Bzik DJ, Gu HM, Tanaka M, Fox BA, Inselburg J (1989) An enlarged largest subunit of Plasmodium falciparum RNA polymerase II defines conserved and variable RNA polymerase domains. Nucleic Acids Res 17:9621–9636

    Article  PubMed  CAS  Google Scholar 

  • Liao SM, Taylor IC, Kingston RE, Young RA (1991) RNA polymerase II carboxy-terminal domain contributes to the response to multiple acidic activators in vitro. Genes Dev 5:2431–2440

    Article  PubMed  CAS  Google Scholar 

  • Licatalosi DD et al (2002) Functional interaction of yeast pre-mRNA 3′ end processing factors with RNA polymerase II. Mol Cell 9:1101–1111

    Article  PubMed  CAS  Google Scholar 

  • Litingtung Y et al (1999) Growth retardation and neonatal lethality in mice with a homozygous deletion in the C-terminal domain of RNA polymerase II. Mol Gen Genet 261:100–105

    Article  PubMed  CAS  Google Scholar 

  • Liu P, Greenleaf AL, Stiller JW (2008) The essential sequence elements required for RNAP II carboxyl-terminal domain function in yeast and their evolutionary conservation. Mol Biol Evol 25:719–727

    Article  PubMed  CAS  Google Scholar 

  • Meininghaus M, Chapman RD, Horndasch M, Eick D (2000) Conditional expression of RNA polymerase II in mammalian cells. Deletion of the carboxyl-terminal domain of the large subunit affects early steps in transcription. J Biol Chem 275:24375–24382

    Article  PubMed  CAS  Google Scholar 

  • Mizzen CA et al (1996) The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell 87:1261–1270

    Article  PubMed  CAS  Google Scholar 

  • Nonet M, Sweetser D, Young RA (1987) Functional redundancy and structural polymorphism in the large subunit of RNA polymerase II. Cell 50:909–915

    Article  PubMed  CAS  Google Scholar 

  • Perkins SL (2008) Molecular systematics of the three protein-coding genes of malaria parasites: corrobative and new evidence for the origins of human malaria. Mitochondrial DNA 19:471–478

    PubMed  CAS  Google Scholar 

  • Perkins SL, Sarkar IN, Carter R (2007) The phylogeny of rodent malaria parasites: simultaneous analysis across three genomes. Infect Genet Evol 7:74–83

    Article  PubMed  CAS  Google Scholar 

  • Phatnani HP, Greenleaf AL (2006) Phosphorylation and functions of the RNA polymerase II CTD. Genes Dev 20:2922–2936

    Article  PubMed  CAS  Google Scholar 

  • Proudfoot NJ, Furger A, Dye MJ (2002) Integrating mRNA processing with transcription. Cell 108:501–512

    Article  PubMed  CAS  Google Scholar 

  • Schroeder SC, Schwer B, Shuman S, Bentley D (2000) Dynamic association of capping enzymes with transcribing RNA polymerase II. Genes Dev 14:2435–2440

    Article  PubMed  CAS  Google Scholar 

  • Stiller JW, Cook MS (2004) Functional unit of the RNA polymerase II C-terminal domain lies within heptapeptide pairs. Eukaryot Cell 3:735–740

    Article  PubMed  CAS  Google Scholar 

  • Stiller JW, McConaughy BL, Hall BD (2000) Evolutionary complementation for polymerase II CTD function. Yeast 16:57–64

    Article  PubMed  CAS  Google Scholar 

  • Volkman SK et al (2007) A genome-wide map of diversity in Plasmodium falciparum. Nature Genet 39:113–119

    Article  PubMed  CAS  Google Scholar 

  • Zorio DA, Bentley DL (2004) The link between mRNA processing and transcription: communication works both ways. Exp Cell Res 296:91–97

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant AI 52390 from the National Institutes of Health to K. W. D. and Medical Scientist Training Program Grant GM07739 and the Paul and Daisy Soros Fellowship to S. P. K. We thank John Stiller for his critical reading of the manuscript. We thank the Malaria Research and Reference Reagent Resource Center (MR4), Dr. X. Su of the NIAID for P. falciparum isolate gDNAs, and Mr. Bryan Falk of the American Museum of Natural History for extracting the P. yoelii, P. berghei, and P. vinckei species and subspecies gDNAs.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, Box 62, New York, NY, 10021, USA

    Sandeep P. Kishore, Thomas J. Templeton & Kirk W. Deitsch

  2. Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY, USA

    Susan L. Perkins

Authors
  1. Sandeep P. Kishore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan L. Perkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas J. Templeton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kirk W. Deitsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kirk W. Deitsch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kishore, S.P., Perkins, S.L., Templeton, T.J. et al. An Unusual Recent Expansion of the C-Terminal Domain of RNA Polymerase II in Primate Malaria Parasites Features a Motif Otherwise Found Only in Mammalian Polymerases. J Mol Evol 68, 706–714 (2009). https://doi.org/10.1007/s00239-009-9245-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-009-9245-2

Keywords

Search

Navigation