Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Apr;15(4):2109–2116. doi: 10.1128/mcb.15.4.2109

A trinucleotide repeat-associated increase in the level of Alu RNA-binding protein occurred during the same period as the major Alu amplification that accompanied anthropoid evolution.

D Y Chang 1, N Sasaki-Tozawa 1, L K Green 1, R J Maraia 1
PMCID: PMC230438  PMID: 7534378

Abstract

Nearly 1 million Alu elements in human DNA were inserted by an RNA-mediated retroposition-amplification process that clearly decelerated about 30 million years ago. Since then, Alu sequences have proliferated at a lower rate, including within the human genome, in which Alu mobility continues to generate genetic variability. Initially derived from 7SL RNA of the signal recognition particle (SRP), Alu became a dominant retroposon while retaining secondary structures found in 7SL RNA. We previously identified a human Alu RNA-binding protein as a homolog of the 14-kDa Alu-specific protein of SRP and have shown that its expression is associated with accumulation of 3'-processed Alu RNA. Here, we show that in early anthropoids, the gene encoding SRP14 Alu RNA-binding protein was duplicated and that SRP14-homologous sequences currently reside on different human chromosomes. In anthropoids, the active SRP14 gene acquired a GCA trinucleotide repeat in its 3'-coding region that produces SRP14 polypeptides with extended C-terminal tails. A C-->G substitution in this region converted the mouse sequence CCA GCA to GCA GCA in prosimians, which presumably predisposed this locus to GCA expansion in anthropoids and provides a model for other triplet expansions. Moreover, the presence of the trinucleotide repeat in SRP14 DNA and the corresponding C-terminal tail in SRP14 are associated with a significant increase in SRP14 polypeptide and Alu RNA-binding activity. These genetic events occurred during the period in which an acceleration in Alu retroposition was followed by a sharp deceleration, suggesting that Alu repeats coevolved with C-terminal variants of SRP14 in higher primates.

Full Text

The Full Text of this article is available as a PDF (298.7 KB).

Selected References

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

  1. Batzer M. A., Kilroy G. E., Richard P. E., Shaikh T. H., Desselle T. D., Hoppens C. L., Deininger P. L. Structure and variability of recently inserted Alu family members. Nucleic Acids Res. 1990 Dec 11;18(23):6793–6798. doi: 10.1093/nar/18.23.6793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Batzer M. A., Schmid C. W., Deininger P. L. Evolutionary analyses of repetitive DNA sequences. Methods Enzymol. 1993;224:213–232. doi: 10.1016/0076-6879(93)24017-o. [DOI] [PubMed] [Google Scholar]
  3. Bennett K. L., Hill R. E., Pietras D. F., Woodworth-Gutai M., Kane-Haas C., Houston J. M., Heath J. K., Hastie N. D. Most highly repeated dispersed DNA families in the mouse genome. Mol Cell Biol. 1984 Aug;4(8):1561–1571. doi: 10.1128/mcb.4.8.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bovia F., Bui N., Strub K. The heterodimeric subunit SRP9/14 of the signal recognition particle functions as permuted single polypeptide chain. Nucleic Acids Res. 1994 Jun 11;22(11):2028–2035. doi: 10.1093/nar/22.11.2028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Britten R. J., Baron W. F., Stout D. B., Davidson E. H. Sources and evolution of human Alu repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4770–4774. doi: 10.1073/pnas.85.13.4770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Britten R. J. Evidence that most human Alu sequences were inserted in a process that ceased about 30 million years ago. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6148–6150. doi: 10.1073/pnas.91.13.6148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Britten R. J., Stout D. B., Davidson E. H. The current source of human Alu retroposons is a conserved gene shared with Old World monkey. Proc Natl Acad Sci U S A. 1989 May;86(10):3718–3722. doi: 10.1073/pnas.86.10.3718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Caskey C. T., Pizzuti A., Fu Y. H., Fenwick R. G., Jr, Nelson D. L. Triplet repeat mutations in human disease. Science. 1992 May 8;256(5058):784–789. doi: 10.1126/science.1589758. [DOI] [PubMed] [Google Scholar]
  9. Chang D. Y., Maraia R. J. A cellular protein binds B1 and Alu small cytoplasmic RNAs in vitro. J Biol Chem. 1993 Mar 25;268(9):6423–6428. [PubMed] [Google Scholar]
  10. Chang D. Y., Nelson B., Bilyeu T., Hsu K., Darlington G. J., Maraia R. J. A human Alu RNA-binding protein whose expression is associated with accumulation of small cytoplasmic Alu RNA. Mol Cell Biol. 1994 Jun;14(6):3949–3959. doi: 10.1128/mcb.14.6.3949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Daniels G. R., Deininger P. L. Characterization of a third major SINE family of repetitive sequences in the galago genome. Nucleic Acids Res. 1991 Apr 11;19(7):1649–1656. doi: 10.1093/nar/19.7.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Daniels G. R., Fox G. M., Loewensteiner D., Schmid C. W., Deininger P. L. Species-specific homogeneity of the primate Alu family of repeated DNA sequences. Nucleic Acids Res. 1983 Nov 11;11(21):7579–7593. doi: 10.1093/nar/11.21.7579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Economou-Pachnis A., Tsichlis P. N. Insertion of an Alu SINE in the human homologue of the Mlvi-2 locus. Nucleic Acids Res. 1985 Dec 9;13(23):8379–8387. doi: 10.1093/nar/13.23.8379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Englander E. W., Wolffe A. P., Howard B. H. Nucleosome interactions with a human Alu element. Transcriptional repression and effects of template methylation. J Biol Chem. 1993 Sep 15;268(26):19565–19573. [PubMed] [Google Scholar]
  15. Gostout B., Liu Q., Sommer S. S. "Cryptic" repeating triplets of purines and pyrimidines (cRRY(i)) are frequent and polymorphic: analysis of coding cRRY(i) in the proopiomelanocortin (POMC) and TATA-binding protein (TBP) genes. Am J Hum Genet. 1993 Jun;52(6):1182–1190. [PMC free article] [PubMed] [Google Scholar]
  16. Gottlieb E., Steitz J. A. Function of the mammalian La protein: evidence for its action in transcription termination by RNA polymerase III. EMBO J. 1989 Mar;8(3):851–861. doi: 10.1002/j.1460-2075.1989.tb03446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gundelfinger E. D., Krause E., Melli M., Dobberstein B. The organization of the 7SL RNA in the signal recognition particle. Nucleic Acids Res. 1983 Nov 11;11(21):7363–7374. doi: 10.1093/nar/11.21.7363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. He X. P., Bataillé N., Fried H. M. Nuclear export of signal recognition particle RNA is a facilitated process that involves the Alu sequence domain. J Cell Sci. 1994 Apr;107(Pt 4):903–912. doi: 10.1242/jcs.107.4.903. [DOI] [PubMed] [Google Scholar]
  19. Hutchinson G. B., Andrew S. E., McDonald H., Goldberg Y. P., Graham R., Rommens J. M., Hayden M. R. An Alu element retroposition in two families with Huntington disease defines a new active Alu subfamily. Nucleic Acids Res. 1993 Jul 25;21(15):3379–3383. doi: 10.1093/nar/21.15.3379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Jelinek W. R., Schmid C. W. Repetitive sequences in eukaryotic DNA and their expression. Annu Rev Biochem. 1982;51:813–844. doi: 10.1146/annurev.bi.51.070182.004121. [DOI] [PubMed] [Google Scholar]
  22. Jurka J. A new subfamily of recently retroposed human Alu repeats. Nucleic Acids Res. 1993 May 11;21(9):2252–2252. doi: 10.1093/nar/21.9.2252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jurka J., Milosavljevic A. Reconstruction and analysis of human Alu genes. J Mol Evol. 1991 Feb;32(2):105–121. doi: 10.1007/BF02515383. [DOI] [PubMed] [Google Scholar]
  24. Jurka J., Smith T. A fundamental division in the Alu family of repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4775–4778. doi: 10.1073/pnas.85.13.4775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jurka J., Zuckerkandl E. Free left arms as precursor molecules in the evolution of Alu sequences. J Mol Evol. 1991 Jul;33(1):49–56. doi: 10.1007/BF02100195. [DOI] [PubMed] [Google Scholar]
  26. Krayev A. S., Kramerov D. A., Skryabin K. G., Ryskov A. P., Bayev A. A., Georgiev G. P. The nucleotide sequence of the ubiquitous repetitive DNA sequence B1 complementary to the most abundant class of mouse fold-back RNA. Nucleic Acids Res. 1980 Mar 25;8(6):1201–1215. doi: 10.1093/nar/8.6.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Labuda D., Sinnett D., Richer C., Deragon J. M., Striker G. Evolution of mouse B1 repeats: 7SL RNA folding pattern conserved. J Mol Evol. 1991 May;32(5):405–414. doi: 10.1007/BF02101280. [DOI] [PubMed] [Google Scholar]
  28. Labuda D., Zietkiewicz E. Evolution of secondary structure in the family of 7SL-like RNAs. J Mol Evol. 1994 Nov;39(5):506–518. doi: 10.1007/BF00173420. [DOI] [PubMed] [Google Scholar]
  29. Liu W. M., Schmid C. W. Proposed roles for DNA methylation in Alu transcriptional repression and mutational inactivation. Nucleic Acids Res. 1993 Mar 25;21(6):1351–1359. doi: 10.1093/nar/21.6.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Maraia R. J., Chang D. Y., Wolffe A. P., Vorce R. L., Hsu K. The RNA polymerase III terminator used by a B1-Alu element can modulate 3' processing of the intermediate RNA product. Mol Cell Biol. 1992 Apr;12(4):1500–1506. doi: 10.1128/mcb.12.4.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Maraia R. J., Driscoll C. T., Bilyeu T., Hsu K., Darlington G. J. Multiple dispersed loci produce small cytoplasmic Alu RNA. Mol Cell Biol. 1993 Jul;13(7):4233–4241. doi: 10.1128/mcb.13.7.4233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Maraia R. J., Kenan D. J., Keene J. D. Eukaryotic transcription termination factor La mediates transcript release and facilitates reinitiation by RNA polymerase III. Mol Cell Biol. 1994 Mar;14(3):2147–2158. doi: 10.1128/mcb.14.3.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Maraia R. J. The subset of mouse B1 (Alu-equivalent) sequences expressed as small processed cytoplasmic transcripts. Nucleic Acids Res. 1991 Oct 25;19(20):5695–5702. doi: 10.1093/nar/19.20.5695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Maraia R., Zasloff M., Plotz P., Adeniyi-Jones S. Pathway of B1-Alu expression in microinjected oocytes: Xenopus laevis proteins associated with nuclear precursor and processed cytoplasmic RNAs. Mol Cell Biol. 1988 Oct;8(10):4433–4440. doi: 10.1128/mcb.8.10.4433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Martin R. D. Primate palaeontology. Bonanza at Shanghuang. Nature. 1994 Apr 14;368(6472):586–587. doi: 10.1038/368586a0. [DOI] [PubMed] [Google Scholar]
  36. Matera A. G., Hellmann U., Hintz M. F., Schmid C. W. Recently transposed Alu repeats result from multiple source genes. Nucleic Acids Res. 1990 Oct 25;18(20):6019–6023. doi: 10.1093/nar/18.20.6019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Matera A. G., Hellmann U., Schmid C. W. A transpositionally and transcriptionally competent Alu subfamily. Mol Cell Biol. 1990 Oct;10(10):5424–5432. doi: 10.1128/mcb.10.10.5424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mitchell G. A., Labuda D., Fontaine G., Saudubray J. M., Bonnefont J. P., Lyonnet S., Brody L. C., Steel G., Obie C., Valle D. Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):815–819. doi: 10.1073/pnas.88.3.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Muratani K., Hada T., Yamamoto Y., Kaneko T., Shigeto Y., Ohue T., Furuyama J., Higashino K. Inactivation of the cholinesterase gene by Alu insertion: possible mechanism for human gene transposition. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11315–11319. doi: 10.1073/pnas.88.24.11315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ohshima K., Koishi R., Matsuo M., Okada N. Several short interspersed repetitive elements (SINEs) in distant species may have originated from a common ancestral retrovirus: characterization of a squid SINE and a possible mechanism for generation of tRNA-derived retroposons. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6260–6264. doi: 10.1073/pnas.90.13.6260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Okada N. SINEs. Curr Opin Genet Dev. 1991 Dec;1(4):498–504. doi: 10.1016/s0959-437x(05)80198-4. [DOI] [PubMed] [Google Scholar]
  42. Panning B., Smiley J. R. Activation of RNA polymerase III transcription of human Alu elements by herpes simplex virus. Virology. 1994 Jul;202(1):408–417. doi: 10.1006/viro.1994.1357. [DOI] [PubMed] [Google Scholar]
  43. Panning B., Smiley J. R. Activation of RNA polymerase III transcription of human Alu repetitive elements by adenovirus type 5: requirement for the E1b 58-kilodalton protein and the products of E4 open reading frames 3 and 6. Mol Cell Biol. 1993 Jun;13(6):3231–3244. doi: 10.1128/mcb.13.6.3231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Quentin Y. A master sequence related to a free left Alu monomer (FLAM) at the origin of the B1 family in rodent genomes. Nucleic Acids Res. 1994 Jun 25;22(12):2222–2227. doi: 10.1093/nar/22.12.2222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Quentin Y. Fusion of a free left Alu monomer and a free right Alu monomer at the origin of the Alu family in the primate genomes. Nucleic Acids Res. 1992 Feb 11;20(3):487–493. doi: 10.1093/nar/20.3.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Quentin Y. Origin of the Alu family: a family of Alu-like monomers gave birth to the left and the right arms of the Alu elements. Nucleic Acids Res. 1992 Jul 11;20(13):3397–3401. doi: 10.1093/nar/20.13.3397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Quentin Y. The Alu family developed through successive waves of fixation closely connected with primate lineage history. J Mol Evol. 1988;27(3):194–202. doi: 10.1007/BF02100074. [DOI] [PubMed] [Google Scholar]
  48. Rogers J. H. The origin and evolution of retroposons. Int Rev Cytol. 1985;93:187–279. doi: 10.1016/s0074-7696(08)61375-3. [DOI] [PubMed] [Google Scholar]
  49. Ryan S. C., Dugaiczyk A. Newly arisen DNA repeats in primate phylogeny. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9360–9364. doi: 10.1073/pnas.86.23.9360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Sawada I., Schmid C. W. Primate evolution of the alpha-globin gene cluster and its Alu-like repeats. J Mol Biol. 1986 Dec 20;192(4):693–709. doi: 10.1016/0022-2836(86)90022-7. [DOI] [PubMed] [Google Scholar]
  51. Schmid C., Maraia R. Transcriptional regulation and transpositional selection of active SINE sequences. Curr Opin Genet Dev. 1992 Dec;2(6):874–882. doi: 10.1016/s0959-437x(05)80110-8. [DOI] [PubMed] [Google Scholar]
  52. Sharp P. A. Conversion of RNA to DNA in mammals: Alu-like elements and pseudogenes. Nature. 1983 Feb 10;301(5900):471–472. doi: 10.1038/301471a0. [DOI] [PubMed] [Google Scholar]
  53. Shen M. R., Batzer M. A., Deininger P. L. Evolution of the master Alu gene(s). J Mol Evol. 1991 Oct;33(4):311–320. doi: 10.1007/BF02102862. [DOI] [PubMed] [Google Scholar]
  54. Siegel V., Walter P. Each of the activities of signal recognition particle (SRP) is contained within a distinct domain: analysis of biochemical mutants of SRP. Cell. 1988 Jan 15;52(1):39–49. doi: 10.1016/0092-8674(88)90529-6. [DOI] [PubMed] [Google Scholar]
  55. Siegel V., Walter P. Removal of the Alu structural domain from signal recognition particle leaves its protein translocation activity intact. Nature. 1986 Mar 6;320(6057):81–84. doi: 10.1038/320081a0. [DOI] [PubMed] [Google Scholar]
  56. Sinnett D., Richer C., Deragon J. M., Labuda D. Alu RNA secondary structure consists of two independent 7 SL RNA-like folding units. J Biol Chem. 1991 May 15;266(14):8675–8678. [PubMed] [Google Scholar]
  57. Sinnett D., Richer C., Deragon J. M., Labuda D. Alu RNA transcripts in human embryonal carcinoma cells. Model of post-transcriptional selection of master sequences. J Mol Biol. 1992 Aug 5;226(3):689–706. doi: 10.1016/0022-2836(92)90626-u. [DOI] [PubMed] [Google Scholar]
  58. Slagel V., Flemington E., Traina-Dorge V., Bradshaw H., Deininger P. Clustering and subfamily relationships of the Alu family in the human genome. Mol Biol Evol. 1987 Jan;4(1):19–29. doi: 10.1093/oxfordjournals.molbev.a040422. [DOI] [PubMed] [Google Scholar]
  59. Strub K., Moss J., Walter P. Binding sites of the 9- and 14-kilodalton heterodimeric protein subunit of the signal recognition particle (SRP) are contained exclusively in the Alu domain of SRP RNA and contain a sequence motif that is conserved in evolution. Mol Cell Biol. 1991 Aug;11(8):3949–3959. doi: 10.1128/mcb.11.8.3949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Strub K., Walter P. Assembly of the Alu domain of the signal recognition particle (SRP): dimerization of the two protein components is required for efficient binding to SRP RNA. Mol Cell Biol. 1990 Feb;10(2):777–784. doi: 10.1128/mcb.10.2.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Strub K., Walter P. Isolation of a cDNA clone of the 14-kDa subunit of the signal recognition particle by cross-hybridization of differently primed polymerase chain reactions. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9747–9751. doi: 10.1073/pnas.86.24.9747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tiedge H., Chen W., Brosius J. Primary structure, neural-specific expression, and dendritic location of human BC200 RNA. J Neurosci. 1993 Jun;13(6):2382–2390. doi: 10.1523/JNEUROSCI.13-06-02382.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Ullu E., Murphy S., Melli M. Human 7SL RNA consists of a 140 nucleotide middle-repetitive sequence inserted in an alu sequence. Cell. 1982 May;29(1):195–202. doi: 10.1016/0092-8674(82)90103-9. [DOI] [PubMed] [Google Scholar]
  64. Ullu E., Tschudi C. Alu sequences are processed 7SL RNA genes. Nature. 1984 Nov 8;312(5990):171–172. doi: 10.1038/312171a0. [DOI] [PubMed] [Google Scholar]
  65. 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]
  66. Wallace M. R., Andersen L. B., Saulino A. M., Gregory P. E., Glover T. W., Collins F. S. A de novo Alu insertion results in neurofibromatosis type 1. Nature. 1991 Oct 31;353(6347):864–866. doi: 10.1038/353864a0. [DOI] [PubMed] [Google Scholar]
  67. Walter P., Blobel G. Disassembly and reconstitution of signal recognition particle. Cell. 1983 Sep;34(2):525–533. doi: 10.1016/0092-8674(83)90385-9. [DOI] [PubMed] [Google Scholar]
  68. Walter P., Blobel G. Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum. Nature. 1982 Oct 21;299(5885):691–698. doi: 10.1038/299691a0. [DOI] [PubMed] [Google Scholar]
  69. Walter P., Blobel G. Subcellular distribution of signal recognition particle and 7SL-RNA determined with polypeptide-specific antibodies and complementary DNA probe. J Cell Biol. 1983 Dec;97(6):1693–1699. doi: 10.1083/jcb.97.6.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Weiner A. M. An abundant cytoplasmic 7S RNA is complementary to the dominant interspersed middle repetitive DNA sequence family in the human genome. Cell. 1980 Nov;22(1 Pt 1):209–218. doi: 10.1016/0092-8674(80)90169-5. [DOI] [PubMed] [Google Scholar]
  71. Willard C., Nguyen H. T., Schmid C. W. Existence of at least three distinct Alu subfamilies. J Mol Evol. 1987;26(3):180–186. doi: 10.1007/BF02099850. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES