Abstract
The machinery required for the replication of eukaryotic chromosomal DNA is made up of proteins whose function, structure and main interaction partners are evolutionarily conserved. Several new cases have been reported recently, however, in which non-coding RNAs play additional and specialised roles in the initiation of eukaryotic DNA replication in different classes of organisms. These non-coding RNAs include Y RNAs in vertebrate somatic cells, 26T RNA in somatic macronuclei of the ciliate Tetrahymena, and G-rich RNA in the Epstein-Barr DNA tumour virus and its human host cells. Here, I will give an overview of the experimental evidence in favour of roles for these non-coding RNAs in the regulation of eukaryotic DNA replication, and compare and contrast their biosynthesis and mechanisms of action.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- ARS:
-
autonomously replicating sequence
- CDK:
-
cyclin-dependent kinase
- DS:
-
dyad symmetry element
- EBER1:
-
EBV-encoded small nuclear RNA 1
- EBNA1:
-
Epstein Barr virus nuclear antigen 1
- EBV:
-
Epstein Barr virus
- FMRP:
-
fragile X mental retardation protein
- GINS:
-
go-ichi-ni-san (five-one-two-three in Japanese)
- HMG:
-
high mobility group
- hY RNA:
-
human Y RNA
- LR:
-
linking region
- MCM:
-
mini-chromosome maintenance
- ORC:
-
origin recognition complex
- OriP:
-
origin of plasmid replication
- PCNA:
-
proliferating cell nuclear antigen
- rDNA:
-
ribosomal DNA
- RFC:
-
replication factor C
- RGG:
-
arginine/glycine-rich repeats
- RNP:
-
ribonucleoprotein
- RPA:
-
replication protein A
- rRNA:
-
ribosomal RNA
- TIF:
-
type I element binding factor
References
Amaral, P. P. and Mattick, J. S. (2008) Noncoding RNA in development. Mamm Genome, 19, 454–492.
Arias, E. E. and Walter, J. C. (2007) Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev, 21, 497–518.
Bell, S. P. and Dutta, A. (2002) DNA replication in eukaryotic cells. Annu Rev Biochem, 71, 333–374.
Carthew, R. W. and Sontheimer, E. J. (2009) Origins and mechanisms of miRNAs and siRNAs. Cell, 136, 642–655.
Challberg, M. D. and Kelly, T. J. (1989) Animal virus DNA replication. Annu Rev Biochem, 58, 671–717.
Chaudhuri, B., Xu, H., Todorov, I., Dutta, A., and Yates, J. L. (2001) Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein-Barr virus. Proc Natl Acad Sci U S A, 98, 10085–10089.
Chen, X., Quinn, A. M., and Wolin, S. L. (2000) Ro ribonucleoproteins contribute to the resistance of Deinococcus radiodurans to ultraviolet irradiation. Genes Dev, 14, 777–782.
Chen, X., Smith, J. D., Shi, H., Yang, D. D., Flavell, R. A., and Wolin, S. L. (2003) The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian cell survival after UV irradiation. Curr Biol, 13, 2206–2211.
Chen, X. and Wolin, S. L. (2004) The Ro 60 kDa autoantigen: insights into cellular function and role in autoimmunity. J Mol Med, 82, 232–239.
Christov, C. P., Gardiner, T. J., Szüts, D., and Krude, T. (2006) Functional requirement of noncoding Y RNAs for human chromosomal DNA replication. Mol Cell Biol, 26, 6993–7004.
Christov, C. P., Trivier, E., and Krude, T. (2008) Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br J Cancer, 98, 981–988.
Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., and Darnell, R. B. (2001) Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell, 107, 489–499.
Darnell, J. C., Warren, S. T., and Darnell, R. B. (2004) The fragile X mental retardation protein, FMRP, recognizes G-quartets. Ment Retard Dev Disabil Res Rev, 10, 49–52.
DePamphilis, M. L., Blow, J. J., Ghosh, S., Saha, T., Noguchi, K., and Vassilev, A. (2006) Regulating the licensing of DNA replication origins in metazoa. Curr Opin Cell Biol, 18, 231–239.
Dhar, S. K., Yoshida, K., Machida, Y., Khaira, P., Chaudhuri, B., Wohlschlegel, J. A., Leffak, M., Yates, J., and Dutta, A. (2001) Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Cell, 106, 287–296.
Donti, T. R., Datta, S., Sandoval, P. Y., and Kapler, G. M. (2009) Differential targeting of Tetrahymena ORC to ribosomal DNA and non-rDNA replication origins. EMBO J, 28, 223–233.
Farris, A. D., Koelsch, G., Pruijn, G. J., van Venrooij, W. J., and Harley, J. B. (1999) Conserved features of Y RNAs revealed by automated phylogenetic secondary structure analysis. Nucleic Acids Res, 27, 1070–1078.
Farris, A. D., O’Brien, C. A., and Harley, J. B. (1995) Y3 is the most conserved small RNA component of Ro ribonucleoprotein complexes in vertebrate species. Gene, 154, 193–198.
Gardiner, T. J., Christov, C. P., Langley, A. R., and Krude, T. (2009) A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication. RNA, 15, 1375–1385.
Ghildiyal, M. and Zamore, P. D. (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet, 10, 94–108.
Green, C. D., Long, K. S., Shi, H., and Wolin, S. L. (1998) Binding of the 60-kDa Ro autoantigen to Y RNAs: evidence for recognition in the major groove of a conserved helix. RNA, 4, 750–765.
Hendrick, J. P., Wolin, S. L., Rinke, J., Lerner, M. R., and Steitz, J. A. (1981) Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Mol Cell Biol, 1, 1138–1149.
Hogg, J. R. and Collins, K. (2008) Structured non-coding RNAs and the RNP Renaissance. Curr Opin Chem Biol, 12, 684–689.
Huppert, J. L. (2008) Hunting G-quadruplexes. Biochimie, 90, 1140–1148.
Krude, T. (2000) Initiation of human DNA replication in vitro using nuclei from cells arrested at an initiation-competent state. J Biol Chem, 275, 13699–13707.
Krude, T. (2006) Initiation of chromosomal DNA replication in mammalian cell-free systems. Cell Cycle, 5, 2115–2122.
Krude, T., Christov, C. P., Hyrien, O., and Marheineke, K. (2009) Y RNA functions at the initiation step of mammalian chromosomal DNA replication. J Cell Sci, 122, 2836–2845.
Krude, T., Jackman, M., Pines, J., and Laskey, R. A. (1997) Cyclin/Cdk-dependent initiation of DNA replication in a human cell-free system. Cell, 88, 109–119.
Labbe, J. C., Hekimi, S., and Rokeach, L. A. (1999) The levels of the RoRNP-associated Y RNA are dependent upon the presence of ROP-1, the Caenorhabditis elegans Ro60 protein. Genetics, 151, 143–150.
Lerner, M. R., Boyle, J. A., Hardin, J. A., and Steitz, J. A. (1981) Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science, 211, 400–402.
Lindner, S. E. and Sugden, B. (2007) The plasmid replicon of Epstein-Barr virus: mechanistic insights into efficient, licensed, extrachromosomal replication in human cells. Plasmid, 58, 1–12.
Lu, C. C., Wu, C. W., Chang, S. C., Chen, T. Y., Hu, C. R., Yeh, M. Y., Chen, J. Y., and Chen, M. R. (2004) Epstein-Barr virus nuclear antigen 1 is a DNA-binding protein with strong RNA-binding activity. J Gen Virol, 85, 2755–2765.
Lutzmann, M., Maiorano, D., and Mechali, M. (2006) A Cdt1-geminin complex licenses chromatin for DNA replication and prevents rereplication during S phase in Xenopus. EMBO J, 25, 5764–5774.
Lutzmann, M. and Mechali, M. (2008) MCM9 binds Cdt1 and is required for the assembly of prereplication complexes. Mol Cell, 31, 190–200.
Machida, Y. J., Hamlin, J. L., and Dutta, A. (2005) Right place, right time, and only once: replication initiation in metazoans. Cell, 123, 13–24.
Maraia, R., Sakulich, A. L., Brinkmann, E., and Green, E. D. (1996) Gene encoding human Ro-associated autoantigen Y5 RNA. Nucleic Acids Res, 24, 3552–3559.
Maraia, R. J., Sasakitozawa, N., Driscoll, C. T., Green, E. D., and Darlington, G. J. (1994) The human Y4 small cytoplasmic RNA gene is controlled by upstream elements and resides on chromosome 7 with all other hY scRNA genes. Nucleic Acids Res, 22, 3045–3052.
Matera, A. G., Frey, M. R., Margelot, K., and Wolin, S. L. (1995) A perinucleolar compartment contains several RNA polymerase III transcripts as well as the polypyrimidine tract-binding protein, hnRNP I. J Cell Biol, 129, 1181–1193.
Mohammad, M., Saha, S., and Kapler, G. M. (2000) Three different proteins recognize a multifunctional determinant that controls replication initiation, fork arrest and transcription in Tetrahymena. Nucleic Acids Res, 28, 843–851.
Mohammad, M., York, R. D., Hommel, J., and Kapler, G. M. (2003) Characterization of a novel origin recognition complex-like complex: implications for DNA recognition, cell cycle control, and locus-specific gene amplification. Mol Cell Biol, 23, 5005–5017.
Mohammad, M. M., Donti, T. R., Sebastian Yakisich, J., Smith, A. G., and Kapler, G. M. (2007) Tetrahymena ORC contains a ribosomal RNA fragment that participates in rDNA origin recognition. EMBO J, 26, 5048–5060.
Mosig, A., Guofeng, M., Stadler, B. M. R., and Stadler, P. F. (2007) Evolution of the vertebrate Y RNA cluster. Theory Biosci., 129, 9–14.
Nasheuer, H. P., Pospiech, H., and Syväoja, J. (2007) Progress towards the anatomy of the eukaryotic DNA replication fork. In: Lankenau, D. H. (Ed.) Genome Integrity: Facets and Perspectives, Genome Dynamics and Stability, Vol. 1, Berlin-Heidelberg-NewYork, Springer, pp 27–68.
Norseen, J., Thomae, A., Sridharan, V., Aiyar, A., Schepers, A., and Lieberman, P. M. (2008) RNA-dependent recruitment of the origin recognition complex. Embo J, 27, 3024–3035.
Perreault, J., Perreault, J. P., and Boire, G. (2007) The Ro associated Y RNAs in metazoans: evolution and diversification. Mol Biol Evol, 24, 1678–1689.
Ponting, C. P., Oliver, P. L., and Reik, W. (2009) Evolution and functions of long noncoding RNAs. Cell, 136, 629–641.
Pruijn, G. J., Wingens, P. A., Peters, S. L., Thijssen, J. P., and van Venrooij, W. J. (1993) Ro RNP associated Y RNAs are highly conserved among mammals. Biochim Biophys Acta, 1216, 395–401.
Reischmann, K. P., Zhang, Z., and Kapler, G. M. (1999) Long range cooperative interactions regulate the initiation of replication in the Tetrahymena thermophila rDNA minichromosome. Nucleic Acids Res, 27, 3079–3089.
Ritzi, M., Tillack, K., Gerhardt, J., Ott, E., Humme, S., Kremmer, E., Hammerschmidt, W., and Schepers, A. (2003) Complex protein-DNA dynamics at the latent origin of DNA replication of Epstein-Barr virus. J Cell Sci, 116, 3971–3984.
Saha, S. and Kapler, G. M. (2000) Allele-specific protein-DNA interactions between the single-stranded DNA-binding protein, ssA-TIBF, and DNA replication determinants in Tetrahymena. J Mol Biol, 295, 423–439.
Schepers, A., Ritzi, M., Bousset, K., Kremmer, E., Yates, J. L., Harwood, J., Diffley, J. F., and Hammerschmidt, W. (2001) Human origin recognition complex binds to the region of the latent origin of DNA replication of Epstein-Barr virus. EMBO J, 20, 4588–4602.
Sears, J., Kolman, J., Wahl, G. M., and Aiyar, A. (2003) Metaphase chromosome tethering is necessary for the DNA synthesis and maintenance of oriP plasmids but is insufficient for transcription activation by Epstein-Barr nuclear antigen 1. J Virol, 77, 11767–11780.
Snudden, D. K., Hearing, J., Smith, P. R., Grasser, F. A., and Griffin, B. E. (1994) EBNA-1, the major nuclear antigen of Epstein-Barr virus, resembles ‘RGG’ RNA binding proteins. EMBO J, 13, 4840–4847.
Stein, A. J., Fuchs, G., Fu, C., Wolin, S. L., and Reinisch, K. M. (2005) Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity. Cell, 121, 529–539.
Stoeber, K., Mills, A. D., Kubota, Y., Marheineke, K., Krude, T., Romanowski, P., Laskey, R. A., and Williams, G. H. (1998) Cdc6 causes premature entry into S phase in a mammalian cell-free system. EMBO J, 17, 7219–7229.
Szüts, D., Christov, C., Kitching, L., and Krude, T. (2005) Distinct populations of human PCNA are required for initiation of chromosomal DNA replication and concurrent DNA repair. Exp Cell Res, 311, 240–250.
Szüts, D., Kitching, L., Christov, C., Budd, A., Peak-Chew, S., and Krude, T. (2003) RPA is an initiation factor for human chromosomal DNA replication. Nucleic Acids Res, 31, 1725–1734.
Takeda, D. Y. and Dutta, A. (2005) DNA replication and progression through S phase. Oncogene, 24, 2827–2843.
Teunissen, S. W., Kruithof, M. J., Farris, A. D., Harley, J. B., Venrooij, W. J., and Pruijn, G. J. (2000) Conserved features of Y RNAs: a comparison of experimentally derived secondary structures. Nucleic Acids Res, 28, 610–619.
Thomae, A. W., Pich, D., Brocher, J., Spindler, M. P., Berens, C., Hock, R., Hammerschmidt, W., and Schepers, A. (2008) Interaction between HMGA1a and the origin recognition complex creates site-specific replication origins. Proc Natl Acad Sci U S A, 105, 1692–1697.
Umthun, A. R., Hou, Z., Sibenaller, Z. A., Shaiu, W. L., and Dobbs, D. L. (1994) Identification of DNA-binding proteins that recognize a conserved type I repeat sequence in the replication origin region of Tetrahymena rDNA. Nucleic Acids Res, 22, 4432–4440.
van Horn, D. J., Eisenberg, D., O’Brien, C. A., and Wolin, S. L. (1995) Caenorhabditis elegans embryos contain only one major species of Ro RNP. RNA, 1, 293–303.
Waga, S. and Stillman, B. (1998) The DNA replication fork in eukaryotic cells. Annu Rev Biochem, 67, 721–751.
Wolin, S. L. and Cedervall, T. (2002) The La protein. Annu Rev Biochem, 71, 375–403.
Xue, D., Shi, H., Smith, J. D., Chen, X., Noe, D. A., Cedervall, T., Yang, D. D., Eynon, E., Brash, D. E., Kashgarian, M., Flavell, R. A., and Wolin, S. L. (2003) A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen. Proc Natl Acad Sci U S A, 100, 7503–7508.
Acknowledgements
I thank Christo P Christov, Cath Green, Alexander R Langley and Aloys Schepers for critical reading of the manuscript. Research in my laboratory is funded by Cancer Research UK.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Krude, T. (2010). Non-coding RNAs: New Players in the Field of Eukaryotic DNA Replication. In: Nasheuer, HP. (eds) Genome Stability and Human Diseases. Subcellular Biochemistry, vol 50. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3471-7_6
Download citation
DOI: https://doi.org/10.1007/978-90-481-3471-7_6
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-3470-0
Online ISBN: 978-90-481-3471-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)