Polypyrimidine tract binding protein blocks the 5′ splice site-dependent assembly of U2AF and the presplicelosomal E complex

被引:124
作者
Sharma, S
Falick, AM
Black, DL
机构
[1] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA
[2] Univ Calif Berkeley, HHMI Mass Spectrometry Lab, Berkeley, CA 94720 USA
[3] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
关键词
D O I
10.1016/j.molcel.2005.07.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Polypyrimidine tract binding protein (PTB) represses some alternatively spliced exons by direct occlusion of splice sites. In repressing the splicing of the c-src N1 exon, we find that PTB acts by a different mechanism. PTB does not interfere with U1 snRNP binding to the N1 5' splice site. Instead, PTB prevents formation of the prespliceosomal early (E) complex across the intervening intron by preventing the assembly of the splicing factor U2AF on the 3' splice site of exon 4. When the unregulated 5' splice site of the upstream exon 3 is present, U2AF binding is restored and splicing between exons 3 and 4 proceeds in spite of the N1 exon bound PTB. Thus, rather than directly blocking the N1 splice sites, PTB prevents the 5' splice site-dependent assembly of U2AF into the E complex. This mechanism likely occurs in many other alternative exons.
引用
收藏
页码:485 / 496
页数:12
相关论文
共 78 条
  • [61] Mechanisms of fidelity in pre-mRNA splicing
    Reed, R
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (03) : 340 - 345
  • [62] Roles for SR proteins and hnRNP A1 in the regulation of c-src exon N1
    Rooke, N
    Markovtsov, V
    Cagavi, E
    Black, DL
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (06) : 1874 - 1884
  • [63] Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1/mBBP
    Selenko, P
    Gregorovic, G
    Sprangers, R
    Stier, G
    Rhani, Z
    Krämer, A
    Sattler, M
    [J]. MOLECULAR CELL, 2003, 11 (04) : 965 - 976
  • [64] Cell signalling and the control of pre-mRNA splicing
    Shin, C
    Manley, JL
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (09) : 727 - 738
  • [65] DISTINCT BINDING SPECIFICITIES AND FUNCTIONS OF HIGHER EUKARYOTIC POLYPYRIMIDINE TRACT-BINDING PROTEINS
    SINGH, R
    VALCARCEL, J
    GREEN, MR
    [J]. SCIENCE, 1995, 268 (5214) : 1173 - 1176
  • [66] Southby J, 1999, MOL CELL BIOL, V19, P2699
  • [67] Mechanical devices of the spliceosome: Motors, clocks, springs, and things
    Staley, JP
    Guthrie, C
    [J]. CELL, 1998, 92 (03) : 315 - 326
  • [68] Architectural limits on split genes
    Sterner, DA
    Carlo, T
    Berget, SM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (26) : 15081 - 15085
  • [69] SR PROTEINS CAN COMPENSATE FOR THE LOSS OF U1 SNRNP FUNCTIONS IN-VITRO
    TARN, WY
    STEITZ, JA
    [J]. GENES & DEVELOPMENT, 1994, 8 (22) : 2704 - 2717
  • [70] THE PROTEIN SEX-LETHAL ANTAGONIZES THE SPLICING FACTOR U2AF TO REGULATE ALTERNATIVE SPLICING OF TRANSFORMER PREMESSENGER RNA
    VALCARCEL, J
    SINGH, R
    ZAMORE, PD
    GREEN, MR
    [J]. NATURE, 1993, 362 (6416) : 171 - 175