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A mechanism for RNA–RNA splicing and a model for the control of gene expression

Published online by Cambridge University Press:  14 April 2009

Vincent Murray  and
Robin Holliday
Vincent Murray
Affiliation:
National Institute for Medical Research, Mill Hill, London NW7 1AA
Robin Holliday
Affiliation:
National Institute for Medical Research, Mill Hill, London NW7 1AA

Summary

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A mechanism for RNA–RNA splicing is proposed. A species of RNA (‘splicer’ RNA) hybridizes to precursor mRNA across the splice point. This hybridization can be with intron or exon sequences or both. The double-stranded RNA structure precisely indicates to the splicing enzymes the exact location for exon ligation.

A model for the control of gene expression is presented. The regulation of synthesis of different splicer RNAs will also control which precursor mRNA molecules are spliced. The removal of intervening sequences from a precursor mRNA molecule could be both a signal for that molecule to be transported to the cytoplasm and a means of allowing gene expression.

Type
Research Article
Information
Genetics Research , Volume 34 , Issue 2 , October 1979 , pp. 173 - 188
Copyright
Copyright © Cambridge University Press 1979

References

REFERENCES

Akusjarvi, G. & Pettersson, U. (1979). Sequence analysis of adenovirus DNA: Complete nucleotide sequence of the spliced 5′ non-coding region of adenovirus 2 hexon mRNA. Cell 16, 841–850.Google Scholar
Aloni, Y., Dhar, R., Laub, O., Horowitz, M. & Khoury, G. (1977). Novel mechanism for RNA maturation: The leader sequences of SV40mRNA are not transcribed adjacent to the coding sequences. Proceedings of the National Academy of Sciences, U.S.A. 74, 3686–3690.CrossRefGoogle ScholarPubMed
Barnet, T. & Rae, P. M. M. (1979). A 9·6 kb intervening sequence in D. virilis r DNA and sequence homology in r DNA interruptions of diverse species of Drosophila and other diptera. Cell 16, 763–775.CrossRefGoogle Scholar
Benz, W. C. & Berger, H. (1973). Selective allele loss in mixed infections with T4 bacteriophage. Genetics 73, 1–11.CrossRefGoogle ScholarPubMed
Berget, S. M., Moore, C. & Sharp, P. A. (1977). Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proceedings of the National Academy of Sciences, U.S.A. 74, 3171–3175.Google Scholar
Bernard, O., Hozumi, N. & Tonegawa, S. (1978). Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell 15, 1133–1144.CrossRefGoogle ScholarPubMed
Blanchard, J.-M., Weber, J., Jelinek, W. & Darnell, J. E. (1978). In vitro RNA-RNA splicing in adenovirus 2 mRNA formation. Proceedings of the National Academy of Sciences, U.S.A. 75, 5344–5348.Google Scholar
Bonner, J., Garrard, W., Gottesfeld, J., Holmes, D. S., Sevall, J. S. & Wilkes, M. M. (1973). Functional organisation of the mammalian genome. Cold Spring Harbor Symposium of Quantitative Biology 38, 303–310.Google Scholar
Breathneck, R., Benoist, C., O'Hara, K., Gannon, F. & Chambon, P. (1978). Ovalbumin gene: Evidence for a leader sequence in mRNA and DNA sequences at the exon–intron boundaries. Proceedings of the National Academy of Sciences, U.S.A. 75, 4853–4857.Google Scholar
Britten, R. J. & Davidson, E. H. (1969). Gene regulation for higher cells: a theory. Science 165, 349–357.Google Scholar
Catterall, J. F., O'Malley, B. W., Robertson, M. A., Staden, R., Tanaka, Y. & Brownlee, G. G. (1978). Nucleotide sequence homology at 12 intron–exon junctions in the chick ovalbumin gene. Nature 275, 510–515.CrossRefGoogle ScholarPubMed
Chow, L. T., Gelinas, R. E., Broker, T. R. & Roberts, R. J. (1977). An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell 12, 1–8.Google Scholar
Cordell, B., Weiss, S. R., Varmus, H. E. & Bishop, J. M. (1978). At least 104 nucleotides are transposed from the 5′ termini of the Avian Sarcoma Virus genome to the 5′ termini of smaller viral mRNAs. Cell 15, 79–91.CrossRefGoogle Scholar
Crick, F. (1979). Split genes and RNA splicing. Science 204, 264–271.CrossRefGoogle ScholarPubMed
Darnell, J. E. (1978). Implications of RNA–RNA splicing in evolution of eukaryotic cells. Science 202, 1257–1260.Google Scholar
Davidson, E. H. & Britten, R. J. (1973). Organisation, transcription and regulation in the animal genome. Quarterly Review of Biology 48, 565–613.Google Scholar
Dawid, I. B. & Botcham, P. (1977). Sequences homologous to ribosomal insertions occur in the Drosophila genome outside the nucleolus organiser. Proceedings of the National Academy of Sciences, U.S.A. 74, 4233–4237.CrossRefGoogle Scholar
Doolittle, W. F. (1978). Why genes in pieces? Were they ever together? Nature 272, 581–582.Google Scholar
Eliceiri, G. L. (1979). Sensitivity of low molecular weight RNA synthesis to U.V. radiation. Nature 279, 80–81.Google Scholar
Flytzanis, C., Alonso, A., Louis, C., Krieg, L. & Sekeris, C. E. (1978). Association of small nuclear RNA with HN RNA isolated from nuclear ribonucleoprotein complexes carrying HN RNA. FEBS Letters 96, 201–206.CrossRefGoogle Scholar
Gilbert, W. (1978). Why genes in pieces? Nature 271, 501.Google Scholar
Ghosh, P. K., Reddy, V. B., Swinscoe, J., Lebowitz, P. & Weissman, S. M. (1978). Heterogeneity and 5′ terminal structures of the late RNAs of SV40. Journal of Molecular Biology 126, 813–846.CrossRefGoogle Scholar
Glover, D. M. & Hogness, D. S. (1977). A novel arrangement of the 18S and 28S sequences in a repeating unit of Drosophila melanogaster r DNA. Cell 10, 167–176.CrossRefGoogle Scholar
Harris, B. & Roeder, R. G. (1978). Structural relationships of low molecular weight viral RNAs synthesised by RNA Polymerase III in nuclei from adenovirus 2-infected cells. Journal of Biological Chemistry 253, 4120–4127.Google Scholar
Holliday, R. (1964). A mechanism for gene conversion in fungi. Genetical Research, Cambridge 5, 282–304.Google Scholar
Holliday, R. (1974). Molecular aspects of genetic exchange and gene conversion. Genetics 78, 273–289.Google Scholar
Holliday, R. & Pugh, J. E. (1975). DNA modification mechanisms and gene activity during development. Science 187, 226–232.Google Scholar
Jelinek, W. & Leinwand, L. (1978). Low molecular weight RNAs hydrogen bonded to nuclear and cytoplasmic poly(A) terminated RNA from cultured Chinese Hamster Ovary cells. Cell 15, 205–214.CrossRefGoogle ScholarPubMed
Kafatos, F. C., Efstradiadis, A., Forget, B. A. & Weissman, S. M. (1977). Molecular evolution of human and rabbit β-globin mRNAs. Proceedings of the National Academy of Sciences, U.S.A. 74, 5618–5622.CrossRefGoogle ScholarPubMed
Knapp, G., Beckmann, J. J., Johnston, P. A., Fuhrman, S. A. & Abelson, J. (1978). Transcription and processing of intervening sequences in yeast tRNA genes. Cell 14, 221–236.Google Scholar
Kolodny, G. M. (1971). Evidence for transfer of macromolecular RNA between mammalian cells in culture. Experimental Cell Research 65, 313–324.Google Scholar
Konkel, D. A., Tilghman, S. M. & Leder, P. (1978). The sequence of chromosomal mouse β-globin major gene: Homologies in capping, slicing and poly(A) sites. Cell 15, 1125–1132.CrossRefGoogle Scholar
Legon, S., Flavell, A. J., Cowie, A. & Kamen, R. (1979). Amplification in the leader sequence of late polyoma virus mRNAs. Cell 16, 373–388.CrossRefGoogle ScholarPubMed
Lewin, B. (1975 a). Units of transcription and translation: the relationship between heterogeneous RNA and mRNA. Cell 4, 11–20.Google Scholar
Lewin, B. (1975 b). Units of transcription and translation: sequence components of heterogeneous RNA and mRNA. Cell 4, 77–93.Google Scholar
Miller, H. I., Konkel, D. A. & Leder, P. (1978). An intervening sequence of the mouse β-globin major genes shares extensive homology only with β-globin genes. Nature 275, 772–774.Google Scholar
Ohe, K. & Weissman, S. M. (1971). The nucleotide sequence of a low molecular weight RNA from cells infected with adenovirus 2. Journal of Biological Chemistry 246, 6991–7001.CrossRefGoogle ScholarPubMed
Perry, R. P., Bard, E., Hames, B. D., Kelley, D. E. & Schibler, U. (1976). The relationship between heterogeneous RNA and mRNA. Progress in Nucleic Acid Research and Molecular Biology 19, 275–292.Google Scholar
Pitts, J. D. & Simms, J. W. (1977). Permeability of junctions between animal cells. Experimental Cell Research 104, 153–163.Google Scholar
Potter, H. & Dressler, D. (1976). On the mechanism of genetic recombination: electron microscopic observation of recombinant intermediates. Proceedings of the National Academy of Sciences, U.S.A. 73, 3000–3004.CrossRefGoogle Scholar
Preobrazhensky, A. A. & Spirin, A. S. (1978). Informosomes and their protein components: The present state of knowledge. Progress in Nucleic Acid Research and Molecular Biology 21, 1–38.Google Scholar
Sakano, H., Rogers, J. H., Huppi, K., Brack, C., Traunecker, A., Maki, R., Wall, R. & Tonegawa, S. (1979). Domains and the hinge region of an immunoglobulin heavy chain are encoded in separate DNA segments. Nature 277, 627–633.CrossRefGoogle ScholarPubMed
Sekeris, C. E. & Niessing, J. (1975). Evidence for the existence of a structural RNA component in the nuclear ribonucleoprotein particles containing heterogeneous RNA. Biochemical and Biophysical Research Communications 62, 642–650.Google Scholar
Sigal, N. & Alberts, B. (1972). Genetic recombination: The nature of a crossed strand exchange between two homologous DNA molecules. Journal of Molecular Biology 71, 789–793.Google Scholar
Sobell, H. M. (1974). Concerning the stereochemistry of strand equivalence in genetic recombination. In Mechanisms in Recombination (ed. Grell, R. F.), pp. 433–438. New York: Plenum.Google Scholar
Stark, B. C., Kale, R., Bowman, E. J. & Altman, S. (1978). Ribonuclease P: An enzyme with an essential RNA component. Proceedings of the National Academy of Sciences, U.S.A. 75, 3717–3721.CrossRefGoogle ScholarPubMed
Subak-Sharpe, H., Burk, R. R. & Pitts, J. D. (1969). Metabolic cooperation between biochemically marked mammalian cells in tissue culture. Journal of Cellular Science 4, 353–367.Google Scholar
Temin, H. M. (1974). On the origin of RNA tumour viruses. Annual Review of Genetics 8, 155–174.Google Scholar
Tiemeier, D. C., Tilghman, S. M., Polsky, F. I., Seidman, J. G., Leder, A., Edgell, M. H. & Leder, P. (1978). A comparison of two cloned mouse β globin genes and their surrounding and intervening sequences. Cell 14, 237–245.CrossRefGoogle ScholarPubMed
Telghman, S. M., Curtis, P. J., Tiemeier, D. C., Leder, P. & Weissman, C. (1978). The intervening sequence of a mouse β-globin gene is transcribed within the 15S β-globin mRNA precursor. Proceedings of the National Academy of Sciences, U.S.A. 75, 1309–1313.Google Scholar
Tonegawa, S., Maxam, A. M., Tizard, R., Bernard, O. & Gelbert, W. (1978). Sequence of a mouse germ-line gene for a variable region of an immuno-globulin light chain. Proceedings of the National Academy of Sciences, U.S.A. 75, 1485–1489.Google Scholar
Travers, A. (1978). RNA processing. Nature 275, 365.Google Scholar
van den Berg, J., van Ooyen, A., Mantei, N., Schambock, A., Grosveld, G., Flavell, R. A. & Weissman, C. (1978). Comparison of cloned rabbit and mouse β-globin genes showing strong evolutionary divergence of two homologous pairs of introns. Nature 276, 37–44.CrossRefGoogle ScholarPubMed
Weinberg, R. A. & Penman, S. (1968). Small molecular weight monodisperse nuclear RNA. Journal of Molecular Biology 38, 289–304.Google Scholar
Wellauer, P. K. & Dawid, I. B. (1977). The structural organisation of ribosomal DNA in Drosophila melanogaster. Cell 10, 193–212.Google Scholar