Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1995 May 1;14(9):2089–2098. doi: 10.1002/j.1460-2075.1995.tb07200.x

Sm and Sm-like proteins belong to a large family: identification of proteins of the U6 as well as the U1, U2, U4 and U5 snRNPs.

B Séraphin 1
PMCID: PMC398309  PMID: 7744014

Abstract

Several small nuclear RNAs (snRNAs), including the spliceosomal U1, U2, U4 and U5 snRNAs, are associated with Sm proteins. These eight small proteins form a heteromeric complex that binds to snRNAs and plays a major role in small nuclear ribonucleoprotein (snRNP) biogenesis and transport. These proteins are also a major target for autoantibodies in the human disease systemic lupus erythematosus. By sequence comparison I have shown that all the known Sm proteins share a common structural motif which might explain their immunological cross-reactivity. Database searches using this motif uncovered a large number of Sm-like proteins from plants, animals and fungi. These proteins have been grouped in at least 13 different subfamilies. Genes encoding divergent yeast members were cloned and used to produce tagged fusion proteins. Some of these proteins are canonical Sm proteins as they associate with the yeast U1, U2, U4/U6 and U5 snRNAs. Surprisingly, one Sm-like protein was found to be a component of the U6 snRNP. These findings have implications for the structure of the Sm protein complex, spliceosomal snRNP evolution, snRNA transport and modification as well as the involvement of Sm proteins in systemic lupus erythematosus.

Full text

PDF
2089

Images in this article

2091Image
on p.2091
2094Image
on p.2094
2095Image
on p.2095

Selected References

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

  1. Barakat S., Briand J. P., Weber J. C., van Regenmortel M. H., Muller S. Recognition of synthetic peptides of Sm-D autoantigen by lupus sera. Clin Exp Immunol. 1990 Aug;81(2):256–262. doi: 10.1111/j.1365-2249.1990.tb03327.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Branlant C., Krol A., Ebel J. P., Lazar E., Haendler B., Jacob M. U2 RNA shares a structural domain with U1, U4, and U5 RNAs. EMBO J. 1982;1(10):1259–1265. doi: 10.1002/j.1460-2075.1982.tb00022.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brow D. A., Guthrie C. Spliceosomal RNA U6 is remarkably conserved from yeast to mammals. Nature. 1988 Jul 21;334(6179):213–218. doi: 10.1038/334213a0. [DOI] [PubMed] [Google Scholar]
  4. Brunet C., Quan T., Craft J. Comparison of the Drosophila melanogaster, human and murine Sm B cDNAs: evolutionary conservation. Gene. 1993 Feb 28;124(2):269–273. doi: 10.1016/0378-1119(93)90404-q. [DOI] [PubMed] [Google Scholar]
  5. Bruzik J. P., Van Doren K., Hirsh D., Steitz J. A. Trans splicing involves a novel form of small nuclear ribonucleoprotein particles. Nature. 1988 Oct 6;335(6190):559–562. doi: 10.1038/335559a0. [DOI] [PubMed] [Google Scholar]
  6. De Keyser F., Hoch S. O., Takei M., Dang H., De Keyser H., Rokeach L. A., Talal N. Cross-reactivity of the B/B' subunit of the Sm ribonucleoprotein autoantigen with proline-rich polypeptides. Clin Immunol Immunopathol. 1992 Mar;62(3):285–290. doi: 10.1016/0090-1229(92)90104-v. [DOI] [PubMed] [Google Scholar]
  7. Degols G. Functional analysis of the regulatory region adjacent to the cargB gene of Saccharomyces cerevisiae. Nucleotide sequence, gene fusion experiments and cis-dominant regulatory mutation analysis. Eur J Biochem. 1987 Nov 16;169(1):193–200. doi: 10.1111/j.1432-1033.1987.tb13597.x. [DOI] [PubMed] [Google Scholar]
  8. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fabrizio P., Esser S., Kastner B., Lührmann R. Isolation of S. cerevisiae snRNPs: comparison of U1 and U4/U6.U5 to their human counterparts. Science. 1994 Apr 8;264(5156):261–265. doi: 10.1126/science.8146658. [DOI] [PubMed] [Google Scholar]
  10. Fischer U., Heinrich J., van Zee K., Fanning E., Lührmann R. Nuclear transport of U1 snRNP in somatic cells: differences in signal requirement compared with Xenopus laevis oocytes. J Cell Biol. 1994 Jun;125(5):971–980. doi: 10.1083/jcb.125.5.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graack H. R., Grohmann L., Kitakawa M., Goldschmidt-Reisin S. Gene MRP-L4, encoding mitochondrial ribosomal protein YmL4, is indispensable for proper non-respiratory cell functions in yeast. Gene. 1995 Jan 11;152(1):107–112. doi: 10.1016/0378-1119(94)00633-4. [DOI] [PubMed] [Google Scholar]
  12. Green M. R. Biochemical mechanisms of constitutive and regulated pre-mRNA splicing. Annu Rev Cell Biol. 1991;7:559–599. doi: 10.1146/annurev.cb.07.110191.003015. [DOI] [PubMed] [Google Scholar]
  13. Gribskov M., McLachlan A. D., Eisenberg D. Profile analysis: detection of distantly related proteins. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4355–4358. doi: 10.1073/pnas.84.13.4355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guthrie C. Messenger RNA splicing in yeast: clues to why the spliceosome is a ribonucleoprotein. Science. 1991 Jul 12;253(5016):157–163. doi: 10.1126/science.1853200. [DOI] [PubMed] [Google Scholar]
  15. Guthrie C., Patterson B. Spliceosomal snRNAs. Annu Rev Genet. 1988;22:387–419. doi: 10.1146/annurev.ge.22.120188.002131. [DOI] [PubMed] [Google Scholar]
  16. Heinrichs V., Hackl W., Lührmann R. Direct binding of small nuclear ribonucleoprotein G to the Sm site of small nuclear RNA. Ultraviolet light cross-linking of protein G to the AAU stretch within the Sm site (AAUUUGUGG) of U1 small nuclear ribonucleoprotein reconstituted in vitro. J Mol Biol. 1992 Sep 5;227(1):15–28. doi: 10.1016/0022-2836(92)90678-d. [DOI] [PubMed] [Google Scholar]
  17. Hermann H., Fabrizio P., Raker V. A., Foulaki K., Hornig H., Brahms H., Lührmann R. snRNP Sm proteins share two evolutionarily conserved sequence motifs which are involved in Sm protein-protein interactions. EMBO J. 1995 May 1;14(9):2076–2088. doi: 10.1002/j.1460-2075.1995.tb07199.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hirakata M., Craft J., Hardin J. A. Autoantigenic epitopes of the B and D polypeptides of the U1 snRNP. Analysis of domains recognized by the Y12 monoclonal anti-Sm antibody and by patient sera. J Immunol. 1993 Apr 15;150(8 Pt 1):3592–3601. [PubMed] [Google Scholar]
  19. Hirt H., Gartner A., Heberle-Bors E. An alfalfa cDNA encodes a protein with similarity to human snRNP-E. Nucleic Acids Res. 1992 Feb 11;20(3):613–613. doi: 10.1093/nar/20.3.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Izaurralde E., Mattaj I. W. Transport of RNA between nucleus and cytoplasm. Semin Cell Biol. 1992 Aug;3(4):279–288. doi: 10.1016/1043-4682(92)90029-u. [DOI] [PubMed] [Google Scholar]
  22. James J. A., Harley J. B. Linear epitope mapping of an Sm B/B' polypeptide. J Immunol. 1992 Apr 1;148(7):2074–2079. [PubMed] [Google Scholar]
  23. Jansen R., Tollervey D., Hurt E. C. A U3 snoRNP protein with homology to splicing factor PRP4 and G beta domains is required for ribosomal RNA processing. EMBO J. 1993 Jun;12(6):2549–2558. doi: 10.1002/j.1460-2075.1993.tb05910.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jarmolowski A., Mattaj I. W. The determinants for Sm protein binding to Xenopus U1 and U5 snRNAs are complex and non-identical. EMBO J. 1993 Jan;12(1):223–232. doi: 10.1002/j.1460-2075.1993.tb05648.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jones M. H., Guthrie C. Unexpected flexibility in an evolutionarily conserved protein-RNA interaction: genetic analysis of the Sm binding site. EMBO J. 1990 Aug;9(8):2555–2561. doi: 10.1002/j.1460-2075.1990.tb07436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kandels-Lewis S., Séraphin B. Involvement of U6 snRNA in 5' splice site selection. Science. 1993 Dec 24;262(5142):2035–2039. doi: 10.1126/science.8266100. [DOI] [PubMed] [Google Scholar]
  27. Konforti B. B., Konarska M. M. U4/U5/U6 snRNP recognizes the 5' splice site in the absence of U2 snRNP. Genes Dev. 1994 Aug 15;8(16):1962–1973. doi: 10.1101/gad.8.16.1962. [DOI] [PubMed] [Google Scholar]
  28. Koonin E. V., Bork P., Sander C. Yeast chromosome III: new gene functions. EMBO J. 1994 Feb 1;13(3):493–503. doi: 10.1002/j.1460-2075.1994.tb06287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Krämer A. Fractionation of HeLa cell nuclear extracts reveals minor small nuclear ribonucleoprotein particles. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8408–8412. doi: 10.1073/pnas.84.23.8408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lee S. I., Murthy S. C., Trimble J. J., Desrosiers R. C., Steitz J. A. Four novel U RNAs are encoded by a herpesvirus. Cell. 1988 Aug 26;54(5):599–607. doi: 10.1016/s0092-8674(88)80004-7. [DOI] [PubMed] [Google Scholar]
  31. Lerner E. A., Lerner M. R., Janeway C. A., Jr, Steitz J. A. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc Natl Acad Sci U S A. 1981 May;78(5):2737–2741. doi: 10.1073/pnas.78.5.2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lerner M. R., Steitz J. A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5495–5499. doi: 10.1073/pnas.76.11.5495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lesser C. F., Guthrie C. Mutations in U6 snRNA that alter splice site specificity: implications for the active site. Science. 1993 Dec 24;262(5142):1982–1988. doi: 10.1126/science.8266093. [DOI] [PubMed] [Google Scholar]
  34. Lohman T. M., Chao K., Green J. M., Sage S., Runyon G. T. Large-scale purification and characterization of the Escherichia coli rep gene product. J Biol Chem. 1989 Jun 15;264(17):10139–10147. [PubMed] [Google Scholar]
  35. Lygerou Z., Mitchell P., Petfalski E., Séraphin B., Tollervey D. The POP1 gene encodes a protein component common to the RNase MRP and RNase P ribonucleoproteins. Genes Dev. 1994 Jun 15;8(12):1423–1433. doi: 10.1101/gad.8.12.1423. [DOI] [PubMed] [Google Scholar]
  36. Lührmann R., Kastner B., Bach M. Structure of spliceosomal snRNPs and their role in pre-mRNA splicing. Biochim Biophys Acta. 1990 Nov 30;1087(3):265–292. doi: 10.1016/0167-4781(90)90001-i. [DOI] [PubMed] [Google Scholar]
  37. Maroney P. A., Hannon G. J., Denker J. A., Nilsen T. W. The nematode spliced leader RNA participates in trans-splicing as an Sm snRNP. EMBO J. 1990 Nov;9(11):3667–3673. doi: 10.1002/j.1460-2075.1990.tb07578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mattaj I. W. Cap trimethylation of U snRNA is cytoplasmic and dependent on U snRNP protein binding. Cell. 1986 Sep 12;46(6):905–911. doi: 10.1016/0092-8674(86)90072-3. [DOI] [PubMed] [Google Scholar]
  39. Mattaj I. W., De Robertis E. M. Nuclear segregation of U2 snRNA requires binding of specific snRNP proteins. Cell. 1985 Jan;40(1):111–118. doi: 10.1016/0092-8674(85)90314-9. [DOI] [PubMed] [Google Scholar]
  40. Mattaj I. W., Tollervey D., Séraphin B. Small nuclear RNAs in messenger RNA and ribosomal RNA processing. FASEB J. 1993 Jan;7(1):47–53. doi: 10.1096/fasebj.7.1.8422974. [DOI] [PubMed] [Google Scholar]
  41. McAllister G., Roby-Shemkovitz A., Amara S. G., Lerner M. R. cDNA sequence of the rat U snRNP-associated protein N: description of a potential Sm epitope. EMBO J. 1989 Apr;8(4):1177–1181. doi: 10.1002/j.1460-2075.1989.tb03489.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Michaeli S., Roberts T. G., Watkins K. P., Agabian N. Isolation of distinct small ribonucleoprotein particles containing the spliced leader and U2 RNAs of Trypanosoma brucei. J Biol Chem. 1990 Jun 25;265(18):10582–10588. [PubMed] [Google Scholar]
  43. Montzka K. A., Steitz J. A. Additional low-abundance human small nuclear ribonucleoproteins: U11, U12, etc. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8885–8889. doi: 10.1073/pnas.85.23.8885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Nelissen R. L., Will C. L., van Venrooij W. J., Lührmann R. The association of the U1-specific 70K and C proteins with U1 snRNPs is mediated in part by common U snRNP proteins. EMBO J. 1994 Sep 1;13(17):4113–4125. doi: 10.1002/j.1460-2075.1994.tb06729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Newman A. J., Norman C. U5 snRNA interacts with exon sequences at 5' and 3' splice sites. Cell. 1992 Feb 21;68(4):743–754. doi: 10.1016/0092-8674(92)90149-7. [DOI] [PubMed] [Google Scholar]
  46. Orlean P., Albright C., Robbins P. W. Cloning and sequencing of the yeast gene for dolichol phosphate mannose synthase, an essential protein. J Biol Chem. 1988 Nov 25;263(33):17499–17507. [PubMed] [Google Scholar]
  47. Palfi Z., Günzl A., Cross M., Bindereif A. Affinity purification of Trypanosoma brucei small nuclear ribonucleoproteins reveals common and specific protein components. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9097–9101. doi: 10.1073/pnas.88.20.9097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Patton J. R. Formation of pseudouridine in U5 small nuclear RNA. Biochemistry. 1994 Aug 30;33(34):10423–10427. doi: 10.1021/bi00200a025. [DOI] [PubMed] [Google Scholar]
  49. Plessel G., Fischer U., Lührmann R. m3G cap hypermethylation of U1 small nuclear ribonucleoprotein (snRNP) in vitro: evidence that the U1 small nuclear RNA-(guanosine-N2)-methyltransferase is a non-snRNP cytoplasmic protein that requires a binding site on the Sm core domain. Mol Cell Biol. 1994 Jun;14(6):4160–4172. doi: 10.1128/mcb.14.6.4160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Preston R. A., Manolson M. F., Becherer K., Weidenhammer E., Kirkpatrick D., Wright R., Jones E. W. Isolation and characterization of PEP3, a gene required for vacuolar biogenesis in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Dec;11(12):5801–5812. doi: 10.1128/mcb.11.12.5801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Rokeach L. A., Haselby J. A., Hoch S. O. Molecular cloning of a cDNA encoding the human Sm-D autoantigen. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4832–4836. doi: 10.1073/pnas.85.13.4832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Rokeach L. A., Jannatipour M., Haselby J. A., Hoch S. O. Mapping of the immunoreactive domains of a small nuclear ribonucleoprotein-associated Sm-D autoantigen. Clin Immunol Immunopathol. 1992 Dec;65(3):315–324. doi: 10.1016/0090-1229(92)90163-i. [DOI] [PubMed] [Google Scholar]
  53. Rosbash M., Séraphin B. Who's on first? The U1 snRNP-5' splice site interaction and splicing. Trends Biochem Sci. 1991 May;16(5):187–190. doi: 10.1016/0968-0004(91)90073-5. [DOI] [PubMed] [Google Scholar]
  54. Ross J., Reid G. A., Dawes I. W. The nucleotide sequence of the LPD1 gene encoding lipoamide dehydrogenase in Saccharomyces cerevisiae: comparison between eukaryotic and prokaryotic sequences for related enzymes and identification of potential upstream control sites. J Gen Microbiol. 1988 May;134(5):1131–1139. doi: 10.1099/00221287-134-5-1131. [DOI] [PubMed] [Google Scholar]
  55. Rost B., Sander C. Combining evolutionary information and neural networks to predict protein secondary structure. Proteins. 1994 May;19(1):55–72. doi: 10.1002/prot.340190108. [DOI] [PubMed] [Google Scholar]
  56. Rost B., Sander C. Prediction of protein secondary structure at better than 70% accuracy. J Mol Biol. 1993 Jul 20;232(2):584–599. doi: 10.1006/jmbi.1993.1413. [DOI] [PubMed] [Google Scholar]
  57. Roy J., Zheng B., Rymond B. C., Woolford J. L., Jr Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins. Mol Cell Biol. 1995 Jan;15(1):445–455. doi: 10.1128/mcb.15.1.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Rymond B. C. Convergent transcripts of the yeast PRP38-SMD1 locus encode two essential splicing factors, including the D1 core polypeptide of small nuclear ribonucleoprotein particles. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):848–852. doi: 10.1073/pnas.90.3.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Schmauss C., McAllister G., Ohosone Y., Hardin J. A., Lerner M. R. A comparison of snRNP-associated Sm-autoantigens: human N, rat N and human B/B'. Nucleic Acids Res. 1989 Feb 25;17(4):1733–1743. doi: 10.1093/nar/17.4.1733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Seraphin B., Rosbash M. Identification of functional U1 snRNA-pre-mRNA complexes committed to spliceosome assembly and splicing. Cell. 1989 Oct 20;59(2):349–358. doi: 10.1016/0092-8674(89)90296-1. [DOI] [PubMed] [Google Scholar]
  61. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Siliciano P. G., Jones M. H., Guthrie C. Saccharomyces cerevisiae has a U1-like small nuclear RNA with unexpected properties. Science. 1987 Sep 18;237(4821):1484–1487. doi: 10.1126/science.3306922. [DOI] [PubMed] [Google Scholar]
  63. Singh R., Reddy R. Gamma-monomethyl phosphate: a cap structure in spliceosomal U6 small nuclear RNA. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8280–8283. doi: 10.1073/pnas.86.21.8280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Smith V., Barrell B. G. Cloning of a yeast U1 snRNP 70K protein homologue: functional conservation of an RNA-binding domain between humans and yeast. EMBO J. 1991 Sep;10(9):2627–2634. doi: 10.1002/j.1460-2075.1991.tb07805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Stanford D. R., Kehl M., Perry C. A., Holicky E. L., Harvey S. E., Rohleder A. M., Rehder K., Jr, Luhrmann R., Wieben E. D. The complete primary structure of the human snRNP E protein. Nucleic Acids Res. 1988 Nov 25;16(22):10593–10605. doi: 10.1093/nar/16.22.10593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Strub K., Birnstiel M. L. Genetic complementation in the Xenopus oocyte: co-expression of sea urchin histone and U7 RNAs restores 3' processing of H3 pre-mRNA in the oocyte. EMBO J. 1986 Jul;5(7):1675–1682. doi: 10.1002/j.1460-2075.1986.tb04411.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Séraphin B., Kretzner L., Rosbash M. A U1 snRNA:pre-mRNA base pairing interaction is required early in yeast spliceosome assembly but does not uniquely define the 5' cleavage site. EMBO J. 1988 Aug;7(8):2533–2538. doi: 10.1002/j.1460-2075.1988.tb03101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Thomas J. D., Conrad R. C., Blumenthal T. The C. elegans trans-spliced leader RNA is bound to Sm and has a trimethylguanosine cap. Cell. 1988 Aug 12;54(4):533–539. doi: 10.1016/0092-8674(88)90075-x. [DOI] [PubMed] [Google Scholar]
  69. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Thompson J. D., Higgins D. G., Gibson T. J. Improved sensitivity of profile searches through the use of sequence weights and gap excision. Comput Appl Biosci. 1994 Feb;10(1):19–29. doi: 10.1093/bioinformatics/10.1.19. [DOI] [PubMed] [Google Scholar]
  71. Toh-e A., Sahashi Y. The PET18 locus of Saccharomyces cerevisiae: a complex locus containing multiple genes. Yeast. 1985 Dec;1(2):159–171. doi: 10.1002/yea.320010204. [DOI] [PubMed] [Google Scholar]
  72. Tollervey D., Mattaj I. W. Fungal small nuclear ribonucleoproteins share properties with plant and vertebrate U-snRNPs. EMBO J. 1987 Feb;6(2):469–476. doi: 10.1002/j.1460-2075.1987.tb04777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Van Doren K., Hirsh D. Trans-spliced leader RNA exists as small nuclear ribonucleoprotein particles in Caenorhabditis elegans. Nature. 1988 Oct 6;335(6190):556–559. doi: 10.1038/335556a0. [DOI] [PubMed] [Google Scholar]
  74. Wersig C., Bindereif A. Reconstitution of functional mammalian U4 small nuclear ribonucleoprotein: Sm protein binding is not essential for splicing in vitro. Mol Cell Biol. 1992 Apr;12(4):1460–1468. doi: 10.1128/mcb.12.4.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES