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. 1996 Aug 1;317(Pt 3):647–651. doi: 10.1042/bj3170647

Alternative processing of the sarco/endoplasmic reticulum Ca(2+)-ATPase transcripts during muscle differentiation is a specifically regulated process.

L Van den Bosch 1, L Mertens 1, Y Cavaloc 1, M Peterson 1, F Wuytack 1, J Eggermont 1
PMCID: PMC1217535  PMID: 8760345

Abstract

Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2) requires activation of an otherwise inefficient splice process at the 3'-end of the primary gene transcript. We provide evidence that SERCA2 splicing is a specifically regulated process, rather than the result of an increase in general splice efficiency or a decrease in polyadenylation efficiency at the 5'-most polyadenylation site. This is indicated by the fact that changes in general splice and polyadenylation efficiency, as observed during B-cell maturation, did not affect SERCA2 splicing. Furthermore, expression and overexpression studies did not support the hypothesis that changes in the level of the alternative splice factor ASF/SF2 or other arginine and serine rich proteins are sufficient to obtain the regulation of muscle- and neuronal-specific splicing.

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Selected References

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  1. Cavaloc Y., Popielarz M., Fuchs J. P., Gattoni R., Stévenin J. Characterization and cloning of the human splicing factor 9G8: a novel 35 kDa factor of the serine/arginine protein family. EMBO J. 1994 Jun 1;13(11):2639–2649. doi: 10.1002/j.1460-2075.1994.tb06554.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cáceres J. F., Stamm S., Helfman D. M., Krainer A. R. Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors. Science. 1994 Sep 16;265(5179):1706–1709. doi: 10.1126/science.8085156. [DOI] [PubMed] [Google Scholar]
  3. De Jaegere S., Wuytack F., De Smedt H., Van den Bosch L., Casteels R. Alternative processing of the gene transcripts encoding a plasma-membrane and a sarco/endoplasmic reticulum Ca2+ pump during differentiation of BC3H1 muscle cells. Biochim Biophys Acta. 1993 May 28;1173(2):188–194. doi: 10.1016/0167-4781(93)90180-l. [DOI] [PubMed] [Google Scholar]
  4. Eggermont J. A., Wuytack F., Casteels R. Characterization of the mRNAs encoding the gene 2 sarcoplasmic/endoplasmic-reticulum Ca2+ pump in pig smooth muscle. Biochem J. 1990 Mar 15;266(3):901–907. [PMC free article] [PubMed] [Google Scholar]
  5. Eperon I. C., Ireland D. C., Smith R. A., Mayeda A., Krainer A. R. Pathways for selection of 5' splice sites by U1 snRNPs and SF2/ASF. EMBO J. 1993 Sep;12(9):3607–3617. doi: 10.1002/j.1460-2075.1993.tb06034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ge H., Manley J. L. A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro. Cell. 1990 Jul 13;62(1):25–34. doi: 10.1016/0092-8674(90)90236-8. [DOI] [PubMed] [Google Scholar]
  7. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  8. Gunteski-Hamblin A. M., Greeb J., Shull G. E. A novel Ca2+ pump expressed in brain, kidney, and stomach is encoded by an alternative transcript of the slow-twitch muscle sarcoplasmic reticulum Ca-ATPase gene. Identification of cDNAs encoding Ca2+ and other cation-transporting ATPases using an oligonucleotide probe derived from the ATP-binding site. J Biol Chem. 1988 Oct 15;263(29):15032–15040. [PubMed] [Google Scholar]
  9. Himmelspach M., Cavaloc Y., Chebli K., Stévenin J., Gattoni R. Titration of serine/arginine (SR) splicing factors during adenoviral infection modulates E1A pre-mRNA alternative splicing. RNA. 1995 Oct;1(8):794–806. [PMC free article] [PubMed] [Google Scholar]
  10. Krainer A. R., Conway G. C., Kozak D. The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites. Cell. 1990 Jul 13;62(1):35–42. doi: 10.1016/0092-8674(90)90237-9. [DOI] [PubMed] [Google Scholar]
  11. Lee K. A., Bindereif A., Green M. R. A small-scale procedure for preparation of nuclear extracts that support efficient transcription and pre-mRNA splicing. Gene Anal Tech. 1988 Mar-Apr;5(2):22–31. doi: 10.1016/0735-0651(88)90023-4. [DOI] [PubMed] [Google Scholar]
  12. Lytton J., MacLennan D. H. Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca2+-ATPase gene. J Biol Chem. 1988 Oct 15;263(29):15024–15031. [PubMed] [Google Scholar]
  13. Lytton J., Westlin M., Burk S. E., Shull G. E., MacLennan D. H. Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps. J Biol Chem. 1992 Jul 15;267(20):14483–14489. [PubMed] [Google Scholar]
  14. Mayeda A., Krainer A. R. Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2. Cell. 1992 Jan 24;68(2):365–375. doi: 10.1016/0092-8674(92)90477-t. [DOI] [PubMed] [Google Scholar]
  15. Mertens L., Van den Bosch L., Verboomen H., Wuytack F., De Smedt H., Eggermont J. Sequence and spatial requirements for regulated muscle-specific processing of the sarco/endoplasmic reticulum Ca(2+)-ATPase 2 gene transcript. J Biol Chem. 1995 May 5;270(18):11004–11011. doi: 10.1074/jbc.270.18.11004. [DOI] [PubMed] [Google Scholar]
  16. Peterson M. L. Balanced efficiencies of splicing and cleavage-polyadenylation are required for mu-s and mu-m mRNA regulation. Gene Expr. 1992;2(4):319–327. [PMC free article] [PubMed] [Google Scholar]
  17. Peterson M. L., Gimmi E. R., Perry R. P. The developmentally regulated shift from membrane to secreted mu mRNA production is accompanied by an increase in cleavage-polyadenylation efficiency but no measurable change in splicing efficiency. Mol Cell Biol. 1991 Apr;11(4):2324–2327. doi: 10.1128/mcb.11.4.2324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Peterson M. L., Perry R. P. Regulated production of mu m and mu s mRNA requires linkage of the poly(A) addition sites and is dependent on the length of the mu s-mu m intron. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8883–8887. doi: 10.1073/pnas.83.23.8883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Peterson M. L., Perry R. P. The regulated production of mu m and mu s mRNA is dependent on the relative efficiencies of mu s poly(A) site usage and the c mu 4-to-M1 splice. Mol Cell Biol. 1989 Feb;9(2):726–738. doi: 10.1128/mcb.9.2.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Roth M. B., Zahler A. M., Stolk J. A. A conserved family of nuclear phosphoproteins localized to sites of polymerase II transcription. J Cell Biol. 1991 Nov;115(3):587–596. doi: 10.1083/jcb.115.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tarn W. Y., Steitz J. A. SR proteins can compensate for the loss of U1 snRNP functions in vitro. Genes Dev. 1994 Nov 15;8(22):2704–2717. doi: 10.1101/gad.8.22.2704. [DOI] [PubMed] [Google Scholar]
  23. Van den Bosch L., Eggermont J., De Smedt H., Mertens L., Wuytack F., Casteels R. Regulation of splicing is responsible for the expression of the muscle-specific 2a isoform of the sarco/endoplasmic-reticulum Ca(2+)-ATPase. Biochem J. 1994 Sep 1;302(Pt 2):559–566. doi: 10.1042/bj3020559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Verboomen H., Mertens L., Eggermont J., Wuytack F., Van Den Bosch L. Modulation of SERCA2 activity: regulated splicing and interaction with phospholamban. Biosci Rep. 1995 Oct;15(5):307–307. doi: 10.1007/BF01788363. [DOI] [PubMed] [Google Scholar]
  25. Verboomen H., Wuytack F., De Smedt H., Himpens B., Casteels R. Functional difference between SERCA2a and SERCA2b Ca2+ pumps and their modulation by phospholamban. Biochem J. 1992 Sep 1;286(Pt 2):591–595. doi: 10.1042/bj2860591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wuytack F., Raeymaekers L., De Smedt H., Eggermont J. A., Missiaen L., Van Den Bosch L., De Jaegere S., Verboomen H., Plessers L., Casteels R. Ca(2+)-transport ATPases and their regulation in muscle and brain. Ann N Y Acad Sci. 1992 Nov 30;671:82–91. doi: 10.1111/j.1749-6632.1992.tb43786.x. [DOI] [PubMed] [Google Scholar]
  27. Yeakley J. M., Hedjran F., Morfin J. P., Merillat N., Rosenfeld M. G., Emeson R. B. Control of calcitonin/calcitonin gene-related peptide pre-mRNA processing by constitutive intron and exon elements. Mol Cell Biol. 1993 Oct;13(10):5999–6011. doi: 10.1128/mcb.13.10.5999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zahler A. M., Lane W. S., Stolk J. A., Roth M. B. SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev. 1992 May;6(5):837–847. doi: 10.1101/gad.6.5.837. [DOI] [PubMed] [Google Scholar]
  29. de Smedt H., Eggermont J. A., Wuytack F., Parys J. B., Van den Bosch L., Missiaen L., Verbis J., Casteels R. Isoform switching of the sarco(endo)plasmic reticulum Ca2+ pump during differentiation of BC3H1 myoblasts. J Biol Chem. 1991 Apr 15;266(11):7092–7095. [PubMed] [Google Scholar]
  30. de la Bastie D., Wisnewsky C., Schwartz K., Lompré A. M. (Ca2+ + Mg2+)-dependent ATPase mRNA from smooth muscle sarcoplasmic reticulum differs from that in cardiac and fast skeletal muscles. FEBS Lett. 1988 Feb 29;229(1):45–48. doi: 10.1016/0014-5793(88)80794-4. [DOI] [PubMed] [Google Scholar]

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