Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1997 Aug 15;25(16):3228–3234. doi: 10.1093/nar/25.16.3228

Recent evolutionary acquisition of alternative pre-mRNA splicing and 3' processing regulations induced by intronic B2 SINE insertion.

D Michel 1, G Chatelain 1, C Mauduit 1, M Benahmed 1, G Brun 1
PMCID: PMC146886  PMID: 9241235

Abstract

Contrary to the membrane-anchored leukemia inhibitory factor receptor (LIFR), the mouse soluble LIFR is an inhibitor of LIF action, possibly through a ligand titration effect. Two mRNA species encoding the soluble LIFR have been identified. Since the 3'-untranslated end of the shorter form was shown to contain a B2 element, we have examined the possibility that this SINE may be responsible for LIFR mRNA truncation. Transient expression assays, using B2-derived or intron-derived sequences independently or in conjunction, show that the B2 element has fortuitously unmasked a cryptic pre-mRNA 3'processing activity of silent intron sequences. The corresponding locus of the rat genome has been isolated and was shown to be devoid of any retroposon, which may explain why no soluble LIFR has yet been identified in any other species and further indicates that the B2 insertion event in the mouse LIFR gene has occurred recently during evolution. And yet, a tight tissue-specific regulation of alternative synthesis of soluble and membrane-bound LIFR mRNA has already emerged in mice. These results provide striking evidence for the rapid influence of retroposition on genome expression.

Full Text

The Full Text of this article is available as a PDF (250.6 KB).

Selected References

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

  1. Adachi M., Watanabe-Fukunaga R., Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756–1760. doi: 10.1073/pnas.90.5.1756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baltimore D. Retroviruses and retrotransposons: the role of reverse transcription in shaping the eukaryotic genome. Cell. 1985 Mar;40(3):481–482. doi: 10.1016/0092-8674(85)90190-4. [DOI] [PubMed] [Google Scholar]
  3. Barta A., Richards R. I., Baxter J. D., Shine J. Primary structure and evolution of rat growth hormone gene. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4867–4871. doi: 10.1073/pnas.78.8.4867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhatt H., Brunet L. J., Stewart C. L. Uterine expression of leukemia inhibitory factor coincides with the onset of blastocyst implantation. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11408–11412. doi: 10.1073/pnas.88.24.11408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheng L., Gearing D. P., White L. S., Compton D. L., Schooley K., Donovan P. J. Role of leukemia inhibitory factor and its receptor in mouse primordial germ cell growth. Development. 1994 Nov;120(11):3145–3153. doi: 10.1242/dev.120.11.3145. [DOI] [PubMed] [Google Scholar]
  6. Conquet F., Brûlet P. Developmental expression of myeloid leukemia inhibitory factor gene in preimplantation blastocysts and in extraembryonic tissue of mouse embryos. Mol Cell Biol. 1990 Jul;10(7):3801–3805. doi: 10.1128/mcb.10.7.3801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Conquet F., Peyriéras N., Tiret L., Brûlet P. Inhibited gastrulation in mouse embryos overexpressing the leukemia inhibitory factor. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8195–8199. doi: 10.1073/pnas.89.17.8195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edwalds-Gilbert G., Prescott J., Falck-Pedersen E. 3' RNA processing efficiency plays a primary role in generating termination-competent RNA polymerase II elongation complexes. Mol Cell Biol. 1993 Jun;13(6):3472–3480. doi: 10.1128/mcb.13.6.3472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fernandez-Botran R., Vitetta E. S. A soluble, high-affinity, interleukin-4-binding protein is present in the biological fluids of mice. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4202–4206. doi: 10.1073/pnas.87.11.4202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Flanagan J. G., Chan D. C., Leder P. Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell. 1991 Mar 8;64(5):1025–1035. doi: 10.1016/0092-8674(91)90326-t. [DOI] [PubMed] [Google Scholar]
  11. Gearing D. P., Comeau M. R., Friend D. J., Gimpel S. D., Thut C. J., McGourty J., Brasher K. K., King J. A., Gillis S., Mosley B. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. Science. 1992 Mar 13;255(5050):1434–1437. doi: 10.1126/science.1542794. [DOI] [PubMed] [Google Scholar]
  12. Gearing D. P., Gough N. M., King J. A., Hilton D. J., Nicola N. A., Simpson R. J., Nice E. C., Kelso A., Metcalf D. Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF). EMBO J. 1987 Dec 20;6(13):3995–4002. doi: 10.1002/j.1460-2075.1987.tb02742.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gearing D. P., Thut C. J., VandeBos T., Gimpel S. D., Delaney P. B., King J., Price V., Cosman D., Beckmann M. P. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J. 1991 Oct;10(10):2839–2848. doi: 10.1002/j.1460-2075.1991.tb07833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  15. Keller W. No end yet to messenger RNA 3' processing! Cell. 1995 Jun 16;81(6):829–832. doi: 10.1016/0092-8674(95)90001-2. [DOI] [PubMed] [Google Scholar]
  16. Layton M. J., Cross B. A., Metcalf D., Ward L. D., Simpson R. J., Nicola N. A. A major binding protein for leukemia inhibitory factor in normal mouse serum: identification as a soluble form of the cellular receptor. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8616–8620. doi: 10.1073/pnas.89.18.8616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lehrman M. A., Goldstein J. L., Russell D. W., Brown M. S. Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987 Mar 13;48(5):827–835. doi: 10.1016/0092-8674(87)90079-1. [DOI] [PubMed] [Google Scholar]
  18. Li M., Sendtner M., Smith A. Essential function of LIF receptor in motor neurons. Nature. 1995 Dec 14;378(6558):724–727. doi: 10.1038/378724a0. [DOI] [PubMed] [Google Scholar]
  19. Moreira A., Wollerton M., Monks J., Proudfoot N. J. Upstream sequence elements enhance poly(A) site efficiency of the C2 complement gene and are phylogenetically conserved. EMBO J. 1995 Aug 1;14(15):3809–3819. doi: 10.1002/j.1460-2075.1995.tb00050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mülhardt C., Fischer M., Gass P., Simon-Chazottes D., Guénet J. L., Kuhse J., Betz H., Becker C. M. The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron. 1994 Oct;13(4):1003–1015. doi: 10.1016/0896-6273(94)90265-8. [DOI] [PubMed] [Google Scholar]
  21. Narita N., Nishio H., Kitoh Y., Ishikawa Y., Ishikawa Y., Minami R., Nakamura H., Matsuo M. Insertion of a 5' truncated L1 element into the 3' end of exon 44 of the dystrophin gene resulted in skipping of the exon during splicing in a case of Duchenne muscular dystrophy. J Clin Invest. 1993 May;91(5):1862–1867. doi: 10.1172/JCI116402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oberbäumer I. Retroposons do jump: a B2 element recently integrated in an 18S rDNA gene. Nucleic Acids Res. 1992 Feb 25;20(4):671–677. doi: 10.1093/nar/20.4.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Owczarek C. M., Layton M. J., Robb L. G., Nicola N. A., Begley C. G. Molecular basis of the soluble and membrane-bound forms of the murine leukemia inhibitory factor receptor alpha-chain. Expression in normal, gestating, and leukemia inhibitory factor nullizygous mice. J Biol Chem. 1996 Mar 8;271(10):5495–5504. doi: 10.1074/jbc.271.10.5495. [DOI] [PubMed] [Google Scholar]
  24. Pattanakitsakul S., Zheng J. H., Natsuume-Sakai S., Takahashi M., Nonaka M. Aberrant splicing caused by the insertion of the B2 sequence into an intron of the complement C4 gene is the basis for low C4 production in H-2k mice. J Biol Chem. 1992 Apr 15;267(11):7814–7820. [PubMed] [Google Scholar]
  25. Peterson M. L. Regulated immunoglobulin (Ig) RNA processing does not require specific cis-acting sequences: non-Ig RNA can be alternatively processed in B cells and plasma cells. Mol Cell Biol. 1994 Dec;14(12):7891–7898. doi: 10.1128/mcb.14.12.7891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saksela K., Baltimore D. Negative regulation of immunoglobulin kappa light-chain gene transcription by a short sequence homologous to the murine B1 repetitive element. Mol Cell Biol. 1993 Jun;13(6):3698–3705. doi: 10.1128/mcb.13.6.3698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Samuelson L. C., Wiebauer K., Snow C. M., Meisler M. H. Retroviral and pseudogene insertion sites reveal the lineage of human salivary and pancreatic amylase genes from a single gene during primate evolution. Mol Cell Biol. 1990 Jun;10(6):2513–2520. doi: 10.1128/mcb.10.6.2513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith A. G., Heath J. K., Donaldson D. D., Wong G. G., Moreau J., Stahl M., Rogers D. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature. 1988 Dec 15;336(6200):688–690. doi: 10.1038/336688a0. [DOI] [PubMed] [Google Scholar]
  29. Soares M. B., Schon E., Henderson A., Karathanasis S. K., Cate R., Zeitlin S., Chirgwin J., Efstratiadis A. RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon. Mol Cell Biol. 1985 Aug;5(8):2090–2103. doi: 10.1128/mcb.5.8.2090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stewart C. L., Kaspar P., Brunet L. J., Bhatt H., Gadi I., Köntgen F., Abbondanzo S. J. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature. 1992 Sep 3;359(6390):76–79. doi: 10.1038/359076a0. [DOI] [PubMed] [Google Scholar]
  31. Tanda S., Corces V. G. Retrotransposon-induced overexpression of a homeobox gene causes defects in eye morphogenesis in Drosophila. EMBO J. 1991 Feb;10(2):407–417. doi: 10.1002/j.1460-2075.1991.tb07962.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tomida M., Yamamoto-Yamaguchi Y., Hozumi M. Pregnancy associated increase in mRNA for soluble D-factor/LIF receptor in mouse liver. FEBS Lett. 1993 Nov 15;334(2):193–197. doi: 10.1016/0014-5793(93)81710-h. [DOI] [PubMed] [Google Scholar]
  33. Tomida M., Yamamoto-Yamaguchi Y., Hozumi M. Purification of a factor inducing differentiation of mouse myeloid leukemic M1 cells from conditioned medium of mouse fibroblast L929 cells. J Biol Chem. 1984 Sep 10;259(17):10978–10982. [PubMed] [Google Scholar]
  34. Tomida M., Yamamoto-Yamaguchi Y., Hozumi M. Three different cDNAs encoding mouse D-factor/LIF receptor. J Biochem. 1994 Mar;115(3):557–562. doi: 10.1093/oxfordjournals.jbchem.a124375. [DOI] [PubMed] [Google Scholar]
  35. Wahle E., Keller W. The biochemistry of 3'-end cleavage and polyadenylation of messenger RNA precursors. Annu Rev Biochem. 1992;61:419–440. doi: 10.1146/annurev.bi.61.070192.002223. [DOI] [PubMed] [Google Scholar]
  36. Ware C. B., Horowitz M. C., Renshaw B. R., Hunt J. S., Liggitt D., Koblar S. A., Gliniak B. C., McKenna H. J., Papayannopoulou T., Thoma B. Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Development. 1995 May;121(5):1283–1299. doi: 10.1242/dev.121.5.1283. [DOI] [PubMed] [Google Scholar]
  37. Wehrle-Haller B., Weston J. A. Soluble and cell-bound forms of steel factor activity play distinct roles in melanocyte precursor dispersal and survival on the lateral neural crest migration pathway. Development. 1995 Mar;121(3):731–742. doi: 10.1242/dev.121.3.731. [DOI] [PubMed] [Google Scholar]
  38. Williams R. L., Hilton D. J., Pease S., Willson T. A., Stewart C. L., Gearing D. P., Wagner E. F., Metcalf D., Nicola N. A., Gough N. M. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 1988 Dec 15;336(6200):684–687. doi: 10.1038/336684a0. [DOI] [PubMed] [Google Scholar]
  39. Wu J., Grindlay G. J., Bushel P., Mendelsohn L., Allan M. Negative regulation of the human epsilon-globin gene by transcriptional interference: role of an Alu repetitive element. Mol Cell Biol. 1990 Mar;10(3):1209–1216. doi: 10.1128/mcb.10.3.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yamaguchi-Yamamoto Y., Tomida M., Hozumi M. Pregnancy associated increase in differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF)-binding substance(s) in mouse serum. Leuk Res. 1993 Jun;17(6):515–522. doi: 10.1016/0145-2126(93)90127-7. [DOI] [PubMed] [Google Scholar]
  41. Yoshida K., Juni N., Awasaki T., Tsuriya Y., Shaya N., Hori S. H. Retrotransposon-induced ectopic expression of the Om(2D) gene causes the eye-specific Om(2D) phenotype in Drosophila ananassae. Mol Gen Genet. 1994 Dec 1;245(5):577–587. doi: 10.1007/BF00282220. [DOI] [PubMed] [Google Scholar]
  42. Zupan A. A., Johnson E. M., Jr Evidence for endocytosis-dependent proteolysis in the generation of soluble truncated nerve growth factor receptors by A875 human melanoma cells. J Biol Chem. 1991 Aug 15;266(23):15384–15390. [PubMed] [Google Scholar]
  43. van Steeg H., van Oostrom T. M., van Kranen H. J., van Kreijl C. F. Nucleotide sequence of the rat ornithine decarboxylase gene. Nucleic Acids Res. 1988 Aug 25;16(16):8173–8174. doi: 10.1093/nar/16.16.8173. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES