Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Jul;78(7):4471–4474. doi: 10.1073/pnas.78.7.4471

Novel models for RNA splicing that involve a small nuclear RNA.

Y Ohshima, M Itoh, N Okada, T Miyata
PMCID: PMC319813  PMID: 6170064

Abstract

Nucleotide sequences of mammalian small nuclear RNAs (snRNAs) have been analyzed with a computer program for complementarity with sequences around a splice junction of various eukaryotic mRNA precursors (pre-mRNAs). A region in U2 RNA or some other snRNAs can form base pairs with both exons surrounding an intron of certain pre-mRNAs and, thereby, can align the two junctions leading to correct splicing of the pre-mRNA. These findings suggest that a snRNA such as U2 can be involved in splicing certain pre-mRNAs by pairing with exons, which we we call an "exon model" for splicing, as compared with the model involving U1 RNA presented by Lerner et al. [Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. (1980) Nature (London) 283, 220-224]. We constructed a secondary structure model of U1 RNA and studied the capacity of base pairing with pre-mRNAs on the basis of both primary and secondary structures of U1 RNA. We present an alternative model for splicing that involves U1 RNA, which assumes base pairing of noncontiguous regions of U1 RNA with an intron of a pre-mRNA. Pairing of an snRNA with exons could explain correct matching of the two junctions that bound one and the same intron, which is not explained by pairing with consensus sequences at the ends of an intron as proposed by Lerner et al. Pairing of an intron with U1 RNA and pairing of the surrounding exons with another snRNA such as U2 RNA could take place at the same time to insure specificity of splicing.

Full text

PDF
4471

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avvedimento V. E., Vogeli G., Yamada Y., Maizel J. V., Jr, Pastan I., de Crombrugghe B. Correlation between splicing sites within an intron and their sequence complementarity with U1 RNA. Cell. 1980 Oct;21(3):689–696. doi: 10.1016/0092-8674(80)90432-8. [DOI] [PubMed] [Google Scholar]
  2. Bell G. I., Pictet R. L., Rutter W. J., Cordell B., Tischer E., Goodman H. M. Sequence of the human insulin gene. Nature. 1980 Mar 6;284(5751):26–32. doi: 10.1038/284026a0. [DOI] [PubMed] [Google Scholar]
  3. Bernard O., Hozumi N., Tonegawa S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell. 1978 Dec;15(4):1133–1144. doi: 10.1016/0092-8674(78)90041-7. [DOI] [PubMed] [Google Scholar]
  4. Branlant C., Krol A., Ebel J. P., Lazar E., Gallinaro H., Jacob M., Sri-Widada J., Jeanteur P. Nucleotide sequences of nuclear U1A RNAs from chicken, rat and man. Nucleic Acids Res. 1980 Sep 25;8(18):4143–4154. doi: 10.1093/nar/8.18.4143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ghosh P. K., Reddy V. B., Swinscoe J., Lebowitz P., Weissman S. M. Heterogeneity and 5'-terminal structures of the late RNAs of simian virus 40. J Mol Biol. 1978 Dec 25;126(4):813–846. doi: 10.1016/0022-2836(78)90022-0. [DOI] [PubMed] [Google Scholar]
  6. Harada F., Kato N., Nishimura S. The nucleotide sequence of nuclear 4.8S RNA of mouse cells. Biochem Biophys Res Commun. 1980 Aug 14;95(3):1332–1340. doi: 10.1016/0006-291x(80)91620-4. [DOI] [PubMed] [Google Scholar]
  7. Harada F., Kato N. Nucleotide sequences of 4.5S RNAs associated with poly(A)-containing RNAs of mouse and hamster cells. Nucleic Acids Res. 1980 Mar 25;8(6):1273–1285. doi: 10.1093/nar/8.6.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Honjo T., Obata M., Yamawaki-Katoaka Y., Kataoka T., Kawakami T., Takahashi N., Mano Y. Cloning and complete nucleotide sequence of mouse immunoglobulin gamma 1 chain gene. Cell. 1979 Oct;18(2):559–568. doi: 10.1016/0092-8674(79)90072-2. [DOI] [PubMed] [Google Scholar]
  9. Kinniburgh A. J., Ross J. Processing of the mouse beta-globin mRNA precursor: at least two cleavage-ligation reactions are necessary to excise the larger intervening sequence. Cell. 1979 Aug;17(4):915–921. doi: 10.1016/0092-8674(79)90331-3. [DOI] [PubMed] [Google Scholar]
  10. Konkel D. A., Tilghman S. M., Leder P. The sequence of the chromosomal mouse beta-globin major gene: homologies in capping, splicing and poly(A) sites. Cell. 1978 Dec;15(4):1125–1132. doi: 10.1016/0092-8674(78)90040-5. [DOI] [PubMed] [Google Scholar]
  11. Lerner M. R., Boyle J. A., Mount S. M., Wolin S. L., Steitz J. A. Are snRNPs involved in splicing? Nature. 1980 Jan 10;283(5743):220–224. doi: 10.1038/283220a0. [DOI] [PubMed] [Google Scholar]
  12. Lewin B. Alternatives for splicing: recognizing the ends of introns. Cell. 1980 Nov;22(2 Pt 2):324–326. doi: 10.1016/0092-8674(80)90340-2. [DOI] [PubMed] [Google Scholar]
  13. Lomedico P., Rosenthal N., Efstratidadis A., Gilbert W., Kolodner R., Tizard R. The structure and evolution of the two nonallelic rat preproinsulin genes. Cell. 1979 Oct;18(2):545–558. doi: 10.1016/0092-8674(79)90071-0. [DOI] [PubMed] [Google Scholar]
  14. Murray V., Holliday R. Mechanism for RNA splicing of gene transcripts. FEBS Lett. 1979 Oct 1;106(1):5–7. doi: 10.1016/0014-5793(79)80682-1. [DOI] [PubMed] [Google Scholar]
  15. Nishioka Y., Leder P. The complete sequence of a chromosomal mouse alpha--globin gene reveals elements conserved throughout vertebrate evolution. Cell. 1979 Nov;18(3):875–882. doi: 10.1016/0092-8674(79)90139-9. [DOI] [PubMed] [Google Scholar]
  16. Reddy R., Ro-Choi T. S., Henning D., Busch H. Primary sequence of U-1 nuclear ribonucleic acid of Novikoff hepatoma ascites cells. J Biol Chem. 1974 Oct 25;249(20):6486–6494. [PubMed] [Google Scholar]
  17. Reddy V. B., Thimmappaya B., Dhar R., Subramanian K. N., Zain B. S., Pan J., Ghosh P. K., Celma M. L., Weissman S. M. The genome of simian virus 40. Science. 1978 May 5;200(4341):494–502. doi: 10.1126/science.205947. [DOI] [PubMed] [Google Scholar]
  18. Reymond C., Aglianó A., Spohr G. Electron microscope study of duck globin mRNA precursor crosslinked in situ. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4683–4687. doi: 10.1073/pnas.77.8.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ro-Choi T. S., Redy R., Henning D., Takano T., Taylor C. W., Busch H. Nucleotide sequence of 4.5 S ribonucleic acid of Novikoff hepatoma cell nuclei. J Biol Chem. 1972 May 25;247(10):3205–3222. [PubMed] [Google Scholar]
  20. Shibata H., Ro-Choi T. S., Reddy R., Choi Y. C., Henning D., Busch H. The primary nucleotide sequence of nuclear U-2 ribonucleic acid. The 5'-terminal portion of the molecule. J Biol Chem. 1975 May 25;250(10):3909–3920. [PubMed] [Google Scholar]
  21. Smithies O., Blechl A. E., Denniston-Thompson K., Newell N., Richards J. E., Slightom J. L., Tucker P. W., Blattner F. R. Cloning human fetal gamma globin and mouse alpha-type globin DNA: characterization and partial sequencing. Science. 1978 Dec 22;202(4374):1284–1289. doi: 10.1126/science.725604. [DOI] [PubMed] [Google Scholar]
  22. Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M. Complete nucleotide sequence of the human delta-globin gene. Cell. 1980 Oct;21(3):639–646. doi: 10.1016/0092-8674(80)90427-4. [DOI] [PubMed] [Google Scholar]
  23. Tinoco I., Jr, Borer P. N., Dengler B., Levin M. D., Uhlenbeck O. C., Crothers D. M., Bralla J. Improved estimation of secondary structure in ribonucleic acids. Nat New Biol. 1973 Nov 14;246(150):40–41. doi: 10.1038/newbio246040a0. [DOI] [PubMed] [Google Scholar]
  24. Tucker P. W., Marcu K. B., Newell N., Richards J., Blattner F. R. Sequence of the cloned gene for the constant region of murine gamma 2b immunoglobulin heavy chain. Science. 1979 Dec 14;206(4424):1303–1306. doi: 10.1126/science.117549. [DOI] [PubMed] [Google Scholar]
  25. Weinberg R. A. Nuclear RNA metabolism. Annu Rev Biochem. 1973;42:329–354. doi: 10.1146/annurev.bi.42.070173.001553. [DOI] [PubMed] [Google Scholar]
  26. Yamawaki-Kataoka Y., Kataoka T., Takahashi N., Obata M., Honjo T. Complete nucleotide sequence of immunoglobulin gamma2b chain gene cloned from newborn nouse DNA. Nature. 1980 Feb 21;283(5749):786–789. doi: 10.1038/283786a0. [DOI] [PubMed] [Google Scholar]
  27. Zieve G., Penman S. Small RNA species of the HeLa cell: metabolism and subcellular localization. Cell. 1976 May;8(1):19–31. doi: 10.1016/0092-8674(76)90181-1. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES