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PMID: 7708698 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Distinct functions of SR proteins in recruitment of U1 small nuclear ribonucleoprotein to alternative 5' splice sites.

Zahler AM, Roth MB

Abstract

Alternative splicing of precursor messenger RNAs (pre-mRNAs) is an important mechanism for the regulation of gene expression. The members of the SR protein family of pre-mRNA splicing factors have distinct functions in promoting alternative splice site usage. Here we show that SR proteins are required for the first step of spliceosome assembly, interaction of the U1 small nuclear ribonucleoprotein complex (U1 snRNP) with the 5' splice site of the pre-mRNA. Further, we find that individual SR proteins have distinct abilities to promote interaction of U1 snRNP with alternative 5' splice junctions. These results suggest that SR proteins direct 5' splice site selection by regulation of U1 snRNP assembly onto the pre-mRNA.

MeSH Terms
Alternative Splicing Animals Antigens, Polyomavirus Transforming/biosynthesis Base Sequence Cattle DNA Primers Molecular Sequence Data Nuclear Proteins/isolation & purification,metabolism Phosphoproteins/isolation & purification,metabolism Polymerase Chain Reaction RNA Precursors/isolation & purification,metabolism RNA-Binding Proteins Ribonucleoprotein, U1 Small Nuclear/isolation & purification,metabolism Serine-Arginine Splicing Factors Simian virus 40/genetics Templates, Genetic Thymus Gland/metabolism
Chemicals
Antigens, Polyomavirus Transforming DNA Primers Nuclear Proteins Phosphoproteins RNA Precursors RNA-Binding Proteins Ribonucleoprotein, U1 Small Nuclear Serine-Arginine Splicing Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Zahler A M
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Roth M B
References (32)
32 references, click to expand
  1. SR proteins: a conserved family of pre-mRNA splicing factors.
    Genes Dev. 1992 May;6(5):837-47 PMID: 1577277
  2. Isolation of a complementary DNA that encodes the mammalian splicing factor SC35.
    Science. 1992 Apr 24;256(5056):535-8 PMID: 1373910
  3. Distinct functions of SR proteins in alternative pre-mRNA splicing.
    Science. 1993 Apr 9;260(5105):219-22 PMID: 8385799
  4. Human SR proteins and isolation of a cDNA encoding SRp75.
    Mol Cell Biol. 1993 Jul;13(7):4023-8 PMID: 8321209
  5. A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA.
    Cell. 1993 Jul 16;74(1):105-14 PMID: 8334698
  6. A general two-metal-ion mechanism for catalytic RNA.
    Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6498-502 PMID: 8341661
  7. Specific commitment of different pre-mRNAs to splicing by single SR proteins.
    Nature. 1993 Sep 2;365(6441):82-5 PMID: 8361546
  8. Site-specific cross-linking of mammalian U5 snRNP to the 5' splice site before the first step of pre-mRNA splicing.
    Genes Dev. 1992 Dec;6(12B):2542-53 PMID: 1340469
  9. Pathways for selection of 5' splice sites by U1 snRNPs and SF2/ASF.
    EMBO J. 1993 Sep;12(9):3607-17 PMID: 8253084
  10. A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR proteins and stimulates U2 snRNP binding.
    Genes Dev. 1993 Dec;7(12A):2405-17 PMID: 8253386
  11. Specific interactions between proteins implicated in splice site selection and regulated alternative splicing.
    Cell. 1993 Dec 17;75(6):1061-70 PMID: 8261509
  12. The U5 and U6 small nuclear RNAs as active site components of the spliceosome.
    Science. 1993 Dec 24;262(5142):1989-96 PMID: 8266094
  13. General splicing factor SF2/ASF promotes alternative splicing by binding to an exonic splicing enhancer.
    Genes Dev. 1993 Dec;7(12B):2598-608 PMID: 8276242
  14. Protein-protein interactions and 5'-splice-site recognition in mammalian mRNA precursors.
    Nature. 1994 Mar 10;368(6467):119-24 PMID: 8139654
  15. The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5' splice sites.
    Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3363-7 PMID: 7512732
  16. Split genes and RNA splicing.
    Cell. 1994 Jun 17;77(6):805-15 PMID: 7516265
  17. Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes.
    Nature. 1983 Apr 14;302(5909):591-6 PMID: 6188062
  18. On the origin of RNA splicing and introns.
    Cell. 1985 Sep;42(2):397-400 PMID: 2411416
  19. The generality of self-splicing RNA: relationship to nuclear mRNA splicing.
    Cell. 1986 Jan 31;44(2):207-10 PMID: 2417724
  20. A method for introducing random single point deletions in specific DNA target sequences using oligonucleotides.
    Nucleic Acids Res. 1989 Jun 12;17(11):4015-23 PMID: 2662137
  21. A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro.
    Cell. 1990 Jul 13;62(1):25-34 PMID: 2163768
  22. Autoradiography using storage phosphor technology.
    Electrophoresis. 1990 May;11(5):355-60 PMID: 2194789
  23. Complementation by SR proteins of pre-mRNA splicing reactions depleted of U1 snRNP.
    Science. 1994 Sep 23;265(5180):1866-9 PMID: 8091213
  24. SR proteins can compensate for the loss of U1 snRNP functions in vitro.
    Genes Dev. 1994 Nov 15;8(22):2704-17 PMID: 7958927
  25. Mechanism for cryptic splice site activation during pre-mRNA splicing.
    Proc Natl Acad Sci U S A. 1990 Aug;87(16):6253-7 PMID: 2143583
  26. Biochemical characterization of U2 snRNP auxiliary factor: an essential pre-mRNA splicing factor with a novel intranuclear distribution.
    EMBO J. 1991 Jan;10(1):207-14 PMID: 1824937
  27. Primary structure of the human splicing factor ASF reveals similarities with Drosophila regulators.
    Cell. 1991 Jul 26;66(2):373-82 PMID: 1855257
  28. Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70K, and Drosophila splicing regulators.
    Cell. 1991 Jul 26;66(2):383-94 PMID: 1830244
  29. Two members of a conserved family of nuclear phosphoproteins are involved in pre-mRNA splicing.
    Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1301-4 PMID: 1741384
  30. Cloning and domain structure of the mammalian splicing factor U2AF.
    Nature. 1992 Feb 13;355(6361):609-14 PMID: 1538748
  31. The 35-kDa mammalian splicing factor SC35 mediates specific interactions between U1 and U2 small nuclear ribonucleoprotein particles at the 3' splice site.
    Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1725-9 PMID: 1531875
  32. Site-specific modification of pre-mRNA: the 2'-hydroxyl groups at the splice sites.
    Science. 1992 May 15;256(5059):992-7 PMID: 1589782
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1995-03-28
Pages
2642-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42274
Subset
IM
Grants
PHS HHS · 42786-02 · United States
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