Functional properties of p54, a novel SR protein active in constitutive and alternative splicing.
The p54 protein was previously identified by its reactivity with an autoantiserum. We report here that p54 is a new member of the SR family of splicing factors, as judged from its structural, antigenic, and functional characteristics. Consistent with its identification as an SR protein, p54 can function as a constitutive splicing factor in complementing splicing-deficient HeLa cell S100 extract. However, p54 also shows properties distinct from those of other SR family members, p54 can directly interact with the 65-kDa subunit of U2 auxiliary factor (U2AF65), a protein associated with the 3' splice site. In addition, p54 interacts with other SR proteins but does not interact with the U1 small nuclear ribonucleoprotein U1-70K or the 35-kDa subunit of U2 auxiliary factor (U2AF35). This protein-protein interaction profile is different from those of prototypical SR proteins SC35 and ASF/SF2, both of which interact with U1-70K and U2AF35 but not with U2AF65. p54 promotes the use of the distal 5' splice site in E1A pre-mRNA alternative splicing, while the same site is suppressed by ASF/SF2 and SC35. These findings and the differential tissue distribution of p54 suggest that this novel SR protein may participate in regulation of alternative splicing in a tissue- and substrate-dependent manner.
Zhang
W J
WJ
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Wu
J Y
JY
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D018076:DNA, Complementary; D000939:Epitopes / Q000032:analysis; D015870:Gene Expression; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D017924:Nucleopolyhedroviruses; D009928:Organ Specificity; D012322:RNA Precursors / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000068103:Serine-Arginine Splicing Factors; D018411:Spodoptera; D014162:Transfection
D018076:DNA, Complementary; D000939:Epitopes; D009687:Nuclear Proteins; D012322:RNA Precursors; C101745:Sfrs11 protein; D000068103:Serine-Arginine Splicing Factors