A systematic analysis of the factors that determine the strength of pre-mRNA splicing enhancers

被引:139
作者
Graveley, BR [1 ]
Hertel, KJ [1 ]
Maniatis, T [1 ]
机构
[1] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
关键词
pre-mRNA splicing; RNA looping; splicing enhancers; SR proteins;
D O I
10.1093/emboj/17.22.6747
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
We find that the strength of splicing enhancers is determined by the relative activities of the bound serine-arginine (SR)-rich splicing factors, the number of SR proteins within the enhancer complex and the distance between the enhancer and the intron. Remarkably, the splicing activity of the bound SR proteins is directly proportional to the number of RS tetrapeptide sequences within the RS domain. Quantitative analysis of the effects of varying the distance between the enhancer and the intron revealed that the splicing efficiency is directly proportional to the calculated probability of a direct interaction between the enhancer complex and the 3' splice site. These data are consistent with a model in which splicing enhancers function by increasing the local concentration of SR proteins in the vicinity of the nearby intron through RNA looping.
引用
收藏
页码:6747 / 6756
页数:10
相关论文
共 56 条
[1]   THE ROLE OF SPECIFIC PROTEIN-RNA AND PROTEIN-PROTEIN INTERACTIONS IN POSITIVE AND NEGATIVE CONTROL OF PRE-MESSENGER-RNA SPLICING BY TRANSFORMER-2 [J].
AMREIN, H ;
HEDLEY, ML ;
MANIATIS, T .
CELL, 1994, 76 (04) :735-746
[2]   DIFFERENTIAL BINDING OF HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS TO MESSENGER-RNA PRECURSORS PRIOR TO SPLICEOSOME ASSEMBLY INVITRO [J].
BENNETT, M ;
PINOIROMA, S ;
STAKNIS, D ;
DREYFUSS, G ;
REED, R .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (07) :3165-3175
[3]   ACTIVATION OF C-SRC NEURON-SPECIFIC SPLICING BY AN UNUSUAL RNA ELEMENT INVIVO AND INVITRO [J].
BLACK, DL .
CELL, 1992, 69 (05) :795-807
[4]   FUNCTIONAL-ANALYSIS OF PREMESSENGER RNA SPLICING FACTOR SF2/ASF STRUCTURAL DOMAINS [J].
CACERES, JF ;
KRAINER, AR .
EMBO JOURNAL, 1993, 12 (12) :4715-4726
[5]  
Cao WH, 1997, RNA, V3, P1456
[6]   A POTENT GAL4 DERIVATIVE ACTIVATES TRANSCRIPTION AT A DISTANCE INVITRO [J].
CAREY, M ;
LEATHERWOOD, J ;
PTASHNE, M .
SCIENCE, 1990, 247 (4943) :710-712
[7]   A MECHANISM FOR SYNERGISTIC ACTIVATION OF A MAMMALIAN GENE BY GAL4 DERIVATIVES [J].
CAREY, M ;
LIN, YS ;
GREEN, MR ;
PTASHNE, M .
NATURE, 1990, 345 (6273) :361-364
[8]   RNA splicing specificity determined by the coordinated action of RNA recognition motifs in SR proteins [J].
Chandler, SD ;
Mayeda, A ;
Yeakley, JM ;
Krainer, AR ;
Fu, XD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3596-3601
[9]  
FU XD, 1995, RNA, V1, P663
[10]   SPECIFIC COMMITMENT OF DIFFERENT PREMESSENGER RNAS TO SPLICING BY SINGLE SR PROTEINS [J].
FU, XD .
NATURE, 1993, 365 (6441) :82-85