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We analyzed the in vitro splicing pathways of three multi-intervening-sequence (IVS) pre-mRNAs: human beta-globin, which contains two IVSs (K. M. Lang, V. L. van Santen, and R. A. Spritz, EMBO J. 4:1991-1996, 1985); rat alpha-lactalbumin, which contains three IVSs; and murine interleukin-3, which contains four IVSs. We found that there are highly preferred pathways of IVS removal from these multi-IVS pre-mRNAs in vitro. The three IVSs of rat alpha-lactalbumin pre-mRNA were excised sequentially from 5' to 3'; in most molecules, IVS1 was removed first, followed by IVS2 and finally by IVS3. The splicing pathway of interleukin-3 pre-mRNA in vitro was more complex. The four IVSs were excised in a highly preferred temporal order, but the order was not strictly sequential or directional. In most molecules, IVS1 and IVS4 were removed first, either simultaneously or in rapid succession. Subsequently, IVS2 was excised, followed by IVS3. The observed splicing pathways apparently resulted from differences in lag times and maximum excision rates of the different IVSs. We detected no exon skipping during splicing of these transcripts in vitro. These observations have implication for proposed models of splice site selection.
K M Lang, and
R A Spritz
July 1990,
Nucleic acids research,
K M Lang, and
R A Spritz
December 1988,
Genes & development,
K M Lang, and
R A Spritz
March 1994,
Molecular biology reports,
K M Lang, and
R A Spritz
August 1995,
RNA (New York, N.Y.),
K M Lang, and
R A Spritz
July 1987,
Molecular and cellular biology,
K M Lang, and
R A Spritz
December 1992,
Nucleic acids research,
K M Lang, and
R A Spritz
January 1979,
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
K M Lang, and
R A Spritz
July 1981,
The Journal of biological chemistry,
