Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1985 Aug;4(8):1991–1996. doi: 10.1002/j.1460-2075.1985.tb03882.x

The two intervening sequences of human beta- and gamma-globin pre-mRNAs are excised in a preferred temporal order in vitro.

K M Lang, V L van Santen, R A Spritz
PMCID: PMC554452  PMID: 3851741

Abstract

Splicing of complete synthetic human beta- and gamma-globin mRNA precursors (pre-mRNAs) follows a preferred pathway in vitro. In almost all molecules, excision of the first intervening sequence (IVS) is completed before excision of the second IVS initiates. However, in a very small fraction of molecules the order of IVS excision is reversed.

Full text

PDF
1991

Images in this article

1992Fig. 2.
on p.1992
1992Fig. 3.
on p.1992
1993Fig. 4.
on p.1993
1993Fig. 5.
on p.1993
1994Fig. 6.
on p.1994
1995Fig. 7.
on p.1995
1995Fig. 8.
on p.1995

Selected References

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

  1. Antonarakis S. E., Irkin S. H., Cheng T. C., Scott A. F., Sexton J. P., Trusko S. P., Charache S., Kazazian H. H., Jr beta-Thalassemia in American Blacks: novel mutations in the "TATA" box and an acceptor splice site. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1154–1158. doi: 10.1073/pnas.81.4.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
  4. Busslinger M., Moschonas N., Flavell R. A. Beta + thalassemia: aberrant splicing results from a single point mutation in an intron. Cell. 1981 Dec;27(2 Pt 1):289–298. doi: 10.1016/0092-8674(81)90412-8. [DOI] [PubMed] [Google Scholar]
  5. Cheng T. C., Orkin S. H., Antonarakis S. E., Potter M. J., Sexton J. P., Markham A. F., Giardina P. J., Li A., Kazazian H. H., Jr beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects. Proc Natl Acad Sci U S A. 1984 May;81(9):2821–2825. doi: 10.1073/pnas.81.9.2821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dobkin C., Pergolizzi R. G., Bahre P., Bank A. Abnormal splice in a mutant human beta-globin gene not at the site of a mutation. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1184–1188. doi: 10.1073/pnas.80.5.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Donaldson D. S., McNab A. R., Rovera G., Curtis P. J. Nuclear precursor molecules of the two beta-globin mRNAs in Friend erythroleukemia cells. J Biol Chem. 1982 Aug 10;257(15):8655–8660. [PubMed] [Google Scholar]
  9. Farace M. G., Ullu E., Fantoni A., Rossi G. B., Cioe L., Dolei A. Nuclear RNA sequences coding for alpha and beta globins in erythroid cells: evidence for multiple intermediate molecules. Blood. 1979 Jan;53(1):134–141. [PubMed] [Google Scholar]
  10. Goldenberg C. J., Raskas H. J. Splicing patterns of nuclear precursors to the mRNA for adenovirus 2 DNA binding protein. Cell. 1979 Jan;16(1):131–138. doi: 10.1016/0092-8674(79)90194-6. [DOI] [PubMed] [Google Scholar]
  11. Goldsmith M. E., Humphries R. K., Ley T., Cline A., Kantor J. A., Nienhuis A. W. "Silent" nucleotide substitution in a beta+-thalassemia globin gene activates splice site in coding sequence RNA. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2318–2322. doi: 10.1073/pnas.80.8.2318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Green M. R., Maniatis T., Melton D. A. Human beta-globin pre-mRNA synthesized in vitro is accurately spliced in Xenopus oocyte nuclei. Cell. 1983 Mar;32(3):681–694. doi: 10.1016/0092-8674(83)90054-5. [DOI] [PubMed] [Google Scholar]
  13. Grosveld G. C., Koster A., Flavell R. A. A transcription map for the rabbit beta-globin gene. Cell. 1981 Feb;23(2):573–584. doi: 10.1016/0092-8674(81)90153-7. [DOI] [PubMed] [Google Scholar]
  14. Keohavong P., Gattoni R., LeMoullec J. M., Jacob M., Stévenin J. The orderly splicing of the first three leaders of the adenovirus-2 major late transcript. Nucleic Acids Res. 1982 Feb 25;10(4):1215–1229. doi: 10.1093/nar/10.4.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kinniburgh A. J., Ross J. Processing of the mouse beta-globin mRNA precursor: at least two cleavage-ligation reactions are necessary to excise the larger intervening sequence. Cell. 1979 Aug;17(4):915–921. doi: 10.1016/0092-8674(79)90331-3. [DOI] [PubMed] [Google Scholar]
  16. Krainer A. R., Maniatis T., Ruskin B., Green M. R. Normal and mutant human beta-globin pre-mRNAs are faithfully and efficiently spliced in vitro. Cell. 1984 Apr;36(4):993–1005. doi: 10.1016/0092-8674(84)90049-7. [DOI] [PubMed] [Google Scholar]
  17. Lang K. M., Spritz R. A. Cloning specific complete polyadenylylated 3'-terminal cDNA segments. Gene. 1985;33(2):191–196. doi: 10.1016/0378-1119(85)90093-9. [DOI] [PubMed] [Google Scholar]
  18. Lang K. M., Spritz R. A. RNA splice site selection: evidence for a 5' leads to 3' scanning model. Science. 1983 Jun 24;220(4604):1351–1355. doi: 10.1126/science.6304877. [DOI] [PubMed] [Google Scholar]
  19. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Orkin S. H., Kazazian H. H., Jr, Antonarakis S. E., Ostrer H., Goff S. C., Sexton J. P. Abnormal RNA processing due to the exon mutation of beta E-globin gene. Nature. 1982 Dec 23;300(5894):768–769. doi: 10.1038/300768a0. [DOI] [PubMed] [Google Scholar]
  21. Padgett R. A., Hardy S. F., Sharp P. A. Splicing of adenovirus RNA in a cell-free transcription system. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5230–5234. doi: 10.1073/pnas.80.17.5230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Padgett R. A., Konarska M. M., Grabowski P. J., Hardy S. F., Sharp P. A. Lariat RNA's as intermediates and products in the splicing of messenger RNA precursors. Science. 1984 Aug 31;225(4665):898–903. doi: 10.1126/science.6206566. [DOI] [PubMed] [Google Scholar]
  23. Ruskin B., Krainer A. R., Maniatis T., Green M. R. Excision of an intact intron as a novel lariat structure during pre-mRNA splicing in vitro. Cell. 1984 Aug;38(1):317–331. doi: 10.1016/0092-8674(84)90553-1. [DOI] [PubMed] [Google Scholar]
  24. Ryffel G. U., Wyler T., Muellener D. B., Weber R. Identification, organization and processing intermediates of the putative precursors of Xenopus vitellogenin messenger RNA. Cell. 1980 Jan;19(1):53–61. doi: 10.1016/0092-8674(80)90387-6. [DOI] [PubMed] [Google Scholar]
  25. Treisman R., Orkin S. H., Maniatis T. Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes. Nature. 1983 Apr 14;302(5909):591–596. doi: 10.1038/302591a0. [DOI] [PubMed] [Google Scholar]
  26. Treisman R., Proudfoot N. J., Shander M., Maniatis T. A single-base change at a splice site in a beta 0-thalassemic gene causes abnormal RNA splicing. Cell. 1982 Jul;29(3):903–911. doi: 10.1016/0092-8674(82)90452-4. [DOI] [PubMed] [Google Scholar]
  27. Tsai M. J., Ting A. C., Nordstrom J. L., Zimmer W., O'Malley B. W. Processing of high molecular weight ovalbumin and ovomucoid precursor RNAs to messenger RNA. Cell. 1980 Nov;22(1 Pt 1):219–230. doi: 10.1016/0092-8674(80)90170-1. [DOI] [PubMed] [Google Scholar]
  28. Weaver R. F., Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. doi: 10.1093/nar/7.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zeitlin S., Efstratiadis A. In vivo splicing products of the rabbit beta-globin pre-mRNA. Cell. 1984 Dec;39(3 Pt 2):589–602. doi: 10.1016/0092-8674(84)90466-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES