Splice site selection, rate of splicing, and alternative splicing on nascent transcripts.
10.1101/gad.2.6.754
Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

Based on ultrastructural analysis of actively transcribing genes seen in electron micrographs, we present evidence that pre-mRNA splicing occurs with a reasonable frequency on the nascent transcripts of early Drosophila embryo genes and that splice site selection may generally precede polyadenylation. The details of the process observed are in agreement with results from in vitro splicing systems but differ in the more rapid completion of in vivo splicing. For those introns that are removed cotranscriptionally, a series of events is initiated following 3' splice site synthesis, beginning with ribonucleoprotein (RNP) particle formation at the 3' splice site within 48 sec, intron loop formation within 2 min, and splicing within 3 min. The initiation of the process is correlated with 3' splice site synthesis but is independent of 5' splice site synthesis, the position of the intron within the transcript, and the age or length of the transcript. In some cases, introns are removed from the 5' end of a transcript before introns are synthesized at the 3' end, supporting a possible role for the order of transcription in splice site pairing. In general, our observations are consistent with the 'first-come-first-served' principle of splice site selection, although an observed example of exon skipping indicates that alternative splicing possibilities can be accommodated within this general framework.

Bibliography

Beyer, A. L., & Osheim, Y. N. (1988). Splice site selection, rate of splicing, and alternative splicing on nascent transcripts. Genes & Development, 2(6), 754–765.

Authors 2
  1. A L Beyer (first)
  2. Y N Osheim (additional)
References 86 Referenced 386
  1. 10.1016/0092-8674(86)90620-3
  2. {'key': '2021111319465153000_2.6.754.2', 'first-page': '2511', 'article-title': 'Alternative RNA splicing generates transcripts encoding a thorax-specific isoform of Drosophila melanogaster myosin heavy chain.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Alternative RNA splicing generates transcripts encoding a thorax-specific isoform of Drosophila melanogaster myosin heavy chain. (1986)
  3. 10.1007/BF00777473
  4. 10.1016/0092-8674(81)90299-3
  5. 10.1016/0092-8674(80)90236-6
  6. 10.1016/0092-8674(77)90323-3
  7. 10.1002/j.1460-2075.1987.tb02520.x / EMBO J. / An ordered pathway of snRNP binding during mammalian pre-mRNA splicing complex assembly. (1987)
  8. 10.1016/0092-8674(85)90270-3
  9. 10.1016/0022-2836(84)90276-6
  10. 10.1146/annurev.bi.56.070187.002343
  11. 10.1126/science.3890181
  12. {'key': '2021111319465153000_2.6.754.12', 'first-page': '281', 'article-title': 'Multiple interactions between the splicing substrate and small nuclear ribonucleoproteins in spliceosomes.', 'volume': '7', 'year': '1987', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Multiple interactions between the splicing substrate and small nuclear ribonucleoproteins in spliceosomes. (1987)
  13. 10.1126/science.2933810
  14. 10.1101/gad.1.9.1014
  15. 10.1126/science.3952495
  16. 10.1002/j.1460-2075.1987.tb02427.x / EMBO J. / Two spliceosomes can form simultaneously and independently on synthetic double-intron messenger RNA precursors. (1987)
  17. 10.1002/prot.340010302
  18. 10.1016/S0021-9258(17)35679-X / J. Biol. Chem. / Structure of rodent helix-destabilizing protein revealed by cDNA cloning. (1986)
  19. Conway, G., Wooley, J. Bibring, T. and LeStourgeon. W. M. 1988. Ribonucleoproteins package 700 nucleotides of pre-mRNA into a repeating array of regular particles. Mol. Cell. Biol. (in press). (10.1128/MCB.8.7.2884)
  20. 10.1038/297365a0
  21. 10.1016/0092-8674(84)90468-9
  22. 10.1146/annurev.cb.02.110186.002331
  23. 10.1083/jcb.103.4.1153
  24. 10.1073/pnas.82.2.449
  25. 10.1016/0092-8674(84)90427-6
  26. 10.1016/S0092-8674(85)80131-8
  27. 10.1016/0092-8674(86)90812-3
  28. {'key': '2021111319465153000_2.6.754.28', 'first-page': '1294', 'article-title': 'Affinity chromatography of splicing complexes: U2, U5, and U4 + U6 small nuclear ribonucleoprotein particles in the spliceosome.', 'volume': '223', 'year': '1986', 'journal-title': 'Science'} / Science / Affinity chromatography of splicing complexes: U2, U5, and U4 + U6 small nuclear ribonucleoprotein particles in the spliceosome. (1986)
  29. 10.1146/annurev.ge.20.120186.003323
  30. 10.1016/0092-8674(83)90054-5
  31. Hager, E.J. 1987. Ultrastructural aspects of gene expression in Drosophila melanogaster polytene chromatin. Ph.D. dissertation. University of Virginia, Charlottesville, Virginia.
  32. {'key': '2021111319465153000_2.6.754.32', 'first-page': '125', 'article-title': 'The cocoonase zymogen cells of silk moths: A model of terminal differentiation for specific protein synthesis.', 'volume': '1', 'year': '1972', 'journal-title': 'Curr. Topics Dev. Biol.'} / Curr. Topics Dev. Biol. / The cocoonase zymogen cells of silk moths: A model of terminal differentiation for specific protein synthesis. (1972)
  33. 10.1073/pnas.84.22.7928
  34. 10.1093/nar/14.13.5207
  35. 10.1093/nar/10.4.1215
  36. {'key': '2021111319465153000_2.6.754.36', 'first-page': '1822', 'article-title': 'Alternative splicing of alpha A-crystallin RNA.', 'volume': '259', 'year': '1984', 'journal-title': 'J. Biol. Chem.'} / J. Biol. Chem. / Alternative splicing of alpha A-crystallin RNA. (1984)
  37. 10.1016/0092-8674(86)90066-8
  38. 10.1016/0092-8674(87)90614-3
  39. 10.1038/313552a0
  40. 10.1016/0022-2836(87)90032-5
  41. 10.1016/S0021-9258(18)67378-8 / J. Biol. Chem. / Purification and domain structure of core hnRNP proteins A1 and A2 and their relationship to single-stranded DNA-binding proteins. (1986)
  42. 10.1093/nar/14.10.4077
  43. 10.1101/gad.1.6.532
  44. 10.1128/mcb.7.10.3428-3437.1987 / Mol. Cell Biol. / In vitro splicing pathways of pre-mRNAs containing multiple intervening sequences. (1987)
  45. 10.1016/0092-8674(87)90202-9
  46. 10.1083/jcb.100.5.1570
  47. {'key': '2021111319465153000_2.6.754.47', 'first-page': '1346', 'article-title': 'In vitro splicing of kappa immunoglobulin precursor mRNA.', 'volume': '7', 'year': '1987', 'journal-title': 'Mol. Cell Biol.'} / Mol. Cell Biol. / In vitro splicing of kappa immunoglobulin precursor mRNA. (1987)
  48. 10.1038/325673a0
  49. Mann, R.S. 1986. Measurement of transcription elongation rates in Drosophila melanogaster by electron microscopy. M.S. dissertation, University of Virginia, Charlottesville.
  50. 10.1016/0022-2836(83)90005-0
  51. 10.1093/nar/15.14.5613
  52. 10.1016/0092-8674(79)90263-0
  53. 10.1126/science.164.3882.955
  54. {'key': '2021111319465153000_2.6.754.54', 'first-page': '1926', 'article-title': 'Spontaneous splicing mutations at the dihydrofolate reductase locus in Chinese hamster ovary cells.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Spontaneous splicing mutations at the dihydrofolate reductase locus in Chinese hamster ovary cells. (1986)
  55. 10.1016/0092-8674(83)90432-4
  56. 10.1146/annurev.bi.52.070183.002301
  57. 10.1016/S0021-9258(18)43764-7 / J. Biol. Chem. / A single-stranded nucleic acid-binding protein from Artemia salina. II. Interaction with nucleic acids. (1980)
  58. 10.1016/0092-8674(85)90019-4
  59. 10.1002/j.1460-2075.1986.tb04687.x / EMBO J. / Two Drosophila chorion genes terminate transcription in discrete regions near their poly(A) sites. (1986)
  60. 10.1146/annurev.bi.55.070186.005351
  61. 10.1016/0092-8674(87)90564-2
  62. 10.1073/pnas.82.24.8414
  63. 10.1083/jcb.97.1.99
  64. 10.1016/0092-8674(85)90064-9
  65. 10.1016/0092-8674(86)90343-0
  66. 10.1002/j.1460-2075.1986.tb04494.x / EMBO J. / Mammalian single-stranded DNA binding protein UP1 is derived from the hnRNP core protein A1. (1986)
  67. 10.1016/0092-8674(84)90467-7
  68. 10.1016/0092-8674(85)90018-2
  69. 10.1016/S0092-8674(85)80064-7
  70. 10.1016/0092-8674(88)90509-0
  71. 10.1016/0022-2836(84)90263-8
  72. 10.1146/annurev.bi.56.070187.001211
  73. 10.1016/0092-8674(81)90425-6
  74. 10.1093/nar/14.13.5241
  75. 10.1016/0092-8674(83)90542-1
  76. {'key': '2021111319465153000_2.6.754.76', 'first-page': '3194', 'article-title': 'Amount of RNA secondary structure required to induce an alternative splice.', 'volume': '7', 'year': '1987', 'journal-title': 'Mol. Cell Biol.'} / Mol. Cell Biol. / Amount of RNA secondary structure required to induce an alternative splice. (1987)
  77. {'key': '2021111319465153000_2.6.754.77', 'first-page': '1', 'article-title': 'Immunoelectron microscopic localization of snRNPs.', 'volume': '49', 'year': '1983', 'journal-title': 'Biol. Cell'} / Biol. Cell / Immunoelectron microscopic localization of snRNPs. (1983)
  78. Steitz, J.A., D.L. Black, V. Gerke, K.A. Parker, A. K̄amer, D. Frendewey, and W. Keller. 1987. Functions of the abundant U-snRNPs. In Structure and functions of small nuclear ribonucleoprotein particles (ed. M.L. Birnstiel), pp. 115–154. Springer-Verlag, Berlin, Heidelberg, New York. (10.1007/978-3-642-73020-7_5)
  79. 10.1016/0092-8674(86)90518-0
  80. 10.1073/pnas.78.5.2888
  81. 10.1021/bi00288a038
  82. 10.1016/0092-8674(86)90382-X
  83. 10.1016/0092-8674(81)90031-3
  84. 10.1016/0092-8674(84)90466-5
  85. 10.1016/0092-8674(86)90064-4
  86. {'key': '2021111319465153000_2.6.754.86', 'first-page': '2877', 'article-title': 'U1 small nuclear ribonucleoproteins are required early during spliceo-some assembly.', 'volume': '7', 'year': '1987', 'journal-title': 'Mol. Cell Biol.'} / Mol. Cell Biol. / U1 small nuclear ribonucleoproteins are required early during spliceo-some assembly. (1987)
Dates
Type When
Created 18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited 3 years, 9 months ago (Nov. 13, 2021, 10:49 p.m.)
Indexed 1 month, 1 week ago (July 14, 2025, 11:33 p.m.)
Issued 37 years, 2 months ago (June 1, 1988)
Published 37 years, 2 months ago (June 1, 1988)
Published Online 37 years, 2 months ago (June 1, 1988)
Published Print 37 years, 2 months ago (June 1, 1988)
Funders 0

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@article{Beyer_1988, title={Splice site selection, rate of splicing, and alternative splicing on nascent transcripts.}, volume={2}, ISSN={0890-9369}, url={http://dx.doi.org/10.1101/gad.2.6.754}, DOI={10.1101/gad.2.6.754}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Beyer, A L and Osheim, Y N}, year={1988}, month=jun, pages={754–765} }