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. 1985 May;5(5):943–948. doi: 10.1128/mcb.5.5.943

Nonrandom integration of human U4 RNA pseudogenes.

C Bark, K Hammarström, G Westin, U Pettersson
PMCID: PMC366808  PMID: 2582241

Abstract

Four loci for human U4 RNA have been characterized by DNA sequence analysis. The results show that all four loci represent pseudogenes, which are flanked by direct repeats. Three of the pseudogenes, designated U4/5, U4/6, and U4/8, have very similar structures; they are all truncated and contain the first 67 to 68 nucleotides of the U4 RNA sequence. Their properties suggest that they were created by integration of truncated cDNA copies of the U4 RNA into new chromosomal sites. An interesting observation was that their flanking regions exhibit sequence homology. A purine-rich 5'-flanking sequence 12 to 13 nucleotides long is almost perfectly conserved in all three loci. Boxes of homology were also found on the 3' side when the U4/6 and U4/8 loci were compared. The U4/4 locus has a slightly different structure; the pseudogene matches the first 79 nucleotides of U4 RNA, but contains a greater number of mutations than the other pseudogenes. Taken together, the results suggest that a frequently occurring type of pseudogene for human U4 was created by a RNA-mediated mechanism and that the integration sites have features in common.

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Selected References

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

  1. Battey J., Max E. E., McBride W. O., Swan D., Leder P. A processed human immunoglobulin epsilon gene has moved to chromosome 9. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5956–5960. doi: 10.1073/pnas.79.19.5956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  3. Berget S. M. Are U4 small nuclear ribonucleoproteins involved in polyadenylation? Nature. 1984 May 10;309(5964):179–182. doi: 10.1038/309179a0. [DOI] [PubMed] [Google Scholar]
  4. Bernstein L. B., Mount S. M., Weiner A. M. Pseudogenes for human small nuclear RNA U3 appear to arise by integration of self-primed reverse transcripts of the RNA into new chromosomal sites. Cell. 1983 Feb;32(2):461–472. doi: 10.1016/0092-8674(83)90466-x. [DOI] [PubMed] [Google Scholar]
  5. Bringmann P., Appel B., Rinke J., Reuter R., Theissen H., Lührmann R. Evidence for the existence of snRNAs U4 and U6 in a single ribonucleoprotein complex and for their association by intermolecular base pairing. EMBO J. 1984 Jun;3(6):1357–1363. doi: 10.1002/j.1460-2075.1984.tb01977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Busch H., Reddy R., Rothblum L., Choi Y. C. SnRNAs, SnRNPs, and RNA processing. Annu Rev Biochem. 1982;51:617–654. doi: 10.1146/annurev.bi.51.070182.003153. [DOI] [PubMed] [Google Scholar]
  7. Denison R. A., Van Arsdell S. W., Bernstein L. B., Weiner A. M. Abundant pseudogenes for small nuclear RNAs are dispersed in the human genome. Proc Natl Acad Sci U S A. 1981 Feb;78(2):810–814. doi: 10.1073/pnas.78.2.810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Denison R. A., Weiner A. M. Human U1 RNA pseudogenes may be generated by both DNA- and RNA-mediated mechanisms. Mol Cell Biol. 1982 Jul;2(7):815–828. doi: 10.1128/mcb.2.7.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gojobori T., Nei M. Inter-RNA homology and possible roles of small RNAs. J Mol Evol. 1981;17(4):245–250. doi: 10.1007/BF01732762. [DOI] [PubMed] [Google Scholar]
  10. Hammarström K., Westin G., Bark C., Zabielski J., Petterson U. Genes and pseudogenes for human U2 RNA. Implications for the mechanism of pseudogene formation. J Mol Biol. 1984 Oct 25;179(2):157–169. doi: 10.1016/0022-2836(84)90463-7. [DOI] [PubMed] [Google Scholar]
  11. Hammarström K., Westin G., Pettersson U. A pseudogene for human U4 RNA with a remarkable structure. EMBO J. 1982;1(6):737–739. doi: 10.1002/j.1460-2075.1982.tb01239.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hashimoto C., Steitz J. A. U4 and U6 RNAs coexist in a single small nuclear ribonucleoprotein particle. Nucleic Acids Res. 1984 Apr 11;12(7):3283–3293. doi: 10.1093/nar/12.7.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hayashi K. Organization of sequences related to U6 RNA in the human genome. Nucleic Acids Res. 1981 Jul 24;9(14):3379–3388. doi: 10.1093/nar/9.14.3379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hess J. F., Fox M., Schmid C., Shen C. K. Molecular evolution of the human adult alpha-globin-like gene region: insertion and deletion of Alu family repeats and non-Alu DNA sequences. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5970–5974. doi: 10.1073/pnas.80.19.5970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jagadeeswaran P., Forget B. G., Weissman S. M. Short interspersed repetitive DNA elements in eucaryotes: transposable DNA elements generated by reverse transcription of RNA pol III transcripts? Cell. 1981 Oct;26(2 Pt 2):141–142. doi: 10.1016/0092-8674(81)90296-8. [DOI] [PubMed] [Google Scholar]
  16. Karin M., Richards R. I. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene. Nature. 1982 Oct 28;299(5886):797–802. doi: 10.1038/299797a0. [DOI] [PubMed] [Google Scholar]
  17. Krol A., Branlant C., Lazar E., Gallinaro H., Jacob M. Primary and secondary structures of chicken, rat and man nuclear U4 RNAs. Homologies with U1 and U5 RNAs. Nucleic Acids Res. 1981 Jun 25;9(12):2699–2716. doi: 10.1093/nar/9.12.2699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lawn R. M., Fritsch E. F., Parker R. C., Blake G., Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. doi: 10.1016/0092-8674(78)90043-0. [DOI] [PubMed] [Google Scholar]
  19. Lee M. G., Lewis S. A., Wilde C. D., Cowan N. J. Evolutionary history of a multigene family: an expressed human beta-tubulin gene and three processed pseudogenes. Cell. 1983 Jun;33(2):477–487. doi: 10.1016/0092-8674(83)90429-4. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Lund E., Dahlberg J. E. True genes for human U1 small nuclear RNA. Copy number, polymorphism, and methylation. J Biol Chem. 1984 Feb 10;259(3):2013–2021. [PubMed] [Google Scholar]
  22. Manser T., Gesteland R. F. Characterization of small nuclear RNA U1 gene candidates and pseudogenes from the human genome. J Mol Appl Genet. 1981;1(2):117–125. [PubMed] [Google Scholar]
  23. Manser T., Gesteland R. F. Human U1 loci: genes for human U1 RNA have dramatically similar genomic environments. Cell. 1982 May;29(1):257–264. doi: 10.1016/0092-8674(82)90110-6. [DOI] [PubMed] [Google Scholar]
  24. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  25. Mondal H., Hofschneider P. H. Demonstration of free reverse transcriptase in the nuclei of embryonic tissues of the Japanese quail. Biochem Biophys Res Commun. 1983 Oct 14;116(1):303–311. doi: 10.1016/0006-291x(83)90415-1. [DOI] [PubMed] [Google Scholar]
  26. Monstein H. J., Hammarström K., Westin G., Zabielski J., Philipson L., Pettersson U. Loci for human U1 RNA: structural and evolutionary implications. J Mol Biol. 1983 Jun 25;167(2):245–257. doi: 10.1016/s0022-2836(83)80334-9. [DOI] [PubMed] [Google Scholar]
  27. Monstein H. J., Westin G., Philipson L., Pettersson U. A candidate gene for human U1 RNA. EMBO J. 1982;1(1):133–137. doi: 10.1002/j.1460-2075.1982.tb01136.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Moos M., Gallwitz D. Structure of two human beta-actin-related processed genes one of which is located next to a simple repetitive sequence. EMBO J. 1983;2(5):757–761. doi: 10.1002/j.1460-2075.1983.tb01496.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mount S. M., Pettersson I., Hinterberger M., Karmas A., Steitz J. A. The U1 small nuclear RNA-protein complex selectively binds a 5' splice site in vitro. Cell. 1983 Jun;33(2):509–518. doi: 10.1016/0092-8674(83)90432-4. [DOI] [PubMed] [Google Scholar]
  30. Mount S. M., Steitz J. A. Sequence of U1 RNA from Drosophila melanogaster: implications for U1 secondary structure and possible involvement in splicing. Nucleic Acids Res. 1981 Dec 11;9(23):6351–6368. doi: 10.1093/nar/9.23.6351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Murphy J. T., Burgess R. R., Dahlberg J. E., Lund E. Transcription of a gene for human U1 small nuclear RNA. Cell. 1982 May;29(1):265–274. doi: 10.1016/0092-8674(82)90111-8. [DOI] [PubMed] [Google Scholar]
  32. Nilsson B., Uhlén M., Josephson S., Gatenbeck S., Philipson L. An improved positive selection plasmid vector constructed by oligonucleotide mediated mutagenesis. Nucleic Acids Res. 1983 Nov 25;11(22):8019–8030. doi: 10.1093/nar/11.22.8019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Padgett R. A., Mount S. M., Steitz J. A., Sharp P. A. Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein. Cell. 1983 Nov;35(1):101–107. doi: 10.1016/0092-8674(83)90212-x. [DOI] [PubMed] [Google Scholar]
  34. Rogers J., Wall R. A mechanism for RNA splicing. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1877–1879. doi: 10.1073/pnas.77.4.1877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  36. Stenlund A., Perricaudet M., Tiollais P., Pettersson U. Construction of restriction enzyme fragment libraries containing DNA from human adenovirus types 2 and 5. Gene. 1980 Jun;10(1):47–52. doi: 10.1016/0378-1119(80)90142-0. [DOI] [PubMed] [Google Scholar]
  37. Van Arsdell S. W., Denison R. A., Bernstein L. B., Weiner A. M., Manser T., Gesteland R. F. Direct repeats flank three small nuclear RNA pseudogenes in the human genome. Cell. 1981 Oct;26(1 Pt 1):11–17. doi: 10.1016/0092-8674(81)90028-3. [DOI] [PubMed] [Google Scholar]
  38. Van Arsdell S. W., Weiner A. M. Human genes for U2 small nuclear RNA are tandemly repeated. Mol Cell Biol. 1984 Mar;4(3):492–499. doi: 10.1128/mcb.4.3.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Van Arsdell S. W., Weiner A. M. Pseudogenes for human U2 small nuclear RNA do not have a fixed site of 3' truncation. Nucleic Acids Res. 1984 Feb 10;12(3):1463–1471. doi: 10.1093/nar/12.3.1463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Westin G., Monstein H. J., Zabielski J., Philipson L., Pettersson U. Human DNA sequences complementary to the small nuclear RNA U2. Nucleic Acids Res. 1981 Dec 11;9(23):6323–6338. doi: 10.1093/nar/9.23.6323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Westin G., Zabielski J., Hammarström K., Monstein H. J., Bark C., Pettersson U. Clustered genes for human U2 RNA. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3811–3815. doi: 10.1073/pnas.81.12.3811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yang V. W., Lerner M. R., Steitz J. A., Flint S. J. A small nuclear ribonucleoprotein is required for splicing of adenoviral early RNA sequences. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1371–1375. doi: 10.1073/pnas.78.3.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]

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