PROTEIN PHOSPHATASE-1 CAN MODULATE ALTERNATIVE 5' SPLICE-SITE SELECTION IN A HELA SPLICING EXTRACT

被引:46
作者
CARDINALI, B
COHEN, PTW
LAMOND, AI
机构
[1] EUROPEAN MOLEC BIOL LAB,D-69012 HEIDELBERG,GERMANY
[2] UNIV DUNDEE,DEPT BIOCHEM,MRC,PROT PHOSPHORYLAT UNIT,DUNDEE DD1 4HN,SCOTLAND
关键词
PROTEIN PHOSPHORYLATION; PROTEIN PHOSPHATASE; RNA SPLICING; ALTERNATIVE SPLICING;
D O I
10.1016/0014-5793(94)00973-2
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
Recent studies using HeLa in vitro splicing extracts have shown that changes in the relative concentrations of constitutive protein splicing factors can affect the choice between competing 5' splice sites in alternatively spliced mammalian pre-mRNAs. Here we report that treatment of a HeLa splicing extract with human protein phosphatase 1 strongly inhibits formation of mRNA spliced to the distal 5' splice site while stimulating relative use of the proximal 5' splice site. This effect is not observed if spliceosomes assemble prior to protein phosphatase 1 treatment. These data show that alternative splicing in HeLa extracts can be mediated by changes in protein modification as well as by changes in the relative concentration of splicing factors. Changes in protein phosphorylation may thus provide a rapid mechanism for cells to respond to stimuli that require an alteration in alternative splicing patterns.
引用
收藏
页码:276 / 280
页数:5
相关论文
共 32 条
[1]   INHIBITOR-2 FUNCTIONS LIKE A CHAPERONE TO FOLD 3 EXPRESSED ISOFORMS OF MAMMALIAN PROTEIN PHOSPHATASE-1 INTO A CONFORMATION WITH THE SPECIFICITY AND REGULATORY PROPERTIES OF THE NATIVE ENZYME [J].
ALESSI, DR ;
STREET, AJ ;
COHEN, P ;
COHEN, PTW .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 213 (03) :1055-1066
[2]   TARGETED SNRNP DEPLETION REVEALS AN ADDITIONAL ROLE FOR MAMMALIAN U1 SNRNP IN SPLICEOSOME ASSEMBLY [J].
BARABINO, SML ;
BLENCOWE, BJ ;
RYDER, U ;
SPROAT, BS ;
LAMOND, AI .
CELL, 1990, 63 (02) :293-302
[3]   SEQUENCE OF HUMAN PROTEIN-SERINE THREONINE PHOSPHATASE-1 GAMMA AND LOCALIZATION OF THE GENE (PPP1CC) ENCODING IT TO CHROMOSOME BANDS 12Q24.1-Q24.2 [J].
BARKER, HM ;
CRAIG, SP ;
SPURR, NK ;
COHEN, PTW .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1178 (02) :228-233
[4]   PHOSPHORYLATION OF HUMAN HNRNP PROTEIN-A1 ABROGATES INVITRO STRAND ANNEALING ACTIVITY [J].
COBIANCHI, F ;
CALVIO, C ;
STOPPINI, M ;
BUVOLI, M ;
RIVA, S .
NUCLEIC ACIDS RESEARCH, 1993, 21 (04) :949-955
[5]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[6]   PRIMARY STRUCTURE OF THE HUMAN SPLICING FACTOR ASF REVEALS SIMILARITIES WITH DROSOPHILA REGULATORS [J].
GE, H ;
ZUO, P ;
MANLEY, JL .
CELL, 1991, 66 (02) :373-382
[7]   A PROTEIN FACTOR, ASF, CONTROLS CELL-SPECIFIC ALTERNATIVE SPLICING OF SV40 EARLY PRE-MESSENGER-RNA INVITRO [J].
GE, H ;
MANLEY, JL .
CELL, 1990, 62 (01) :25-34
[8]   BIOCHEMICAL-MECHANISMS OF CONSTITUTIVE AND REGULATED PRE-MESSENGER-RNA SPLICING [J].
GREEN, MR .
ANNUAL REVIEW OF CELL BIOLOGY, 1991, 7 :559-599
[9]   FUNCTIONAL EXPRESSION OF CLONED HUMAN SPLICING FACTOR SF2 - HOMOLOGY TO RNA-BINDING PROTEINS, U1-70K, AND DROSOPHILA SPLICING REGULATORS [J].
KRAINER, AR ;
MAYEDA, A ;
KOZAK, D ;
BINNS, G .
CELL, 1991, 66 (02) :383-394
[10]   THE ESSENTIAL PRE-MESSENGER-RNA SPLICING FACTOR-SF2 INFLUENCES 5' SPLICE SITE SELECTION BY ACTIVATING PROXIMAL SITES [J].
KRAINER, AR ;
CONWAY, GC ;
KOZAK, D .
CELL, 1990, 62 (01) :35-42