Modulating alternative splicing by cotranscriptional

被引:16
作者
Gromak, Natalia [1 ]
Talotti, Garriele [2 ]
Proudfoot, Nicholas J. [1 ]
Pagani, Franco [2 ]
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[2] Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy
基金
英国惠康基金; 英国医学研究理事会;
关键词
alternative splicing regulation; RNA polymerase II; alpha-tropomyosin gene; fibronectin gene; ribozyme;
D O I
10.1261/rna.615508
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
Cotranscriptional cleavage mediated by a hammerhead ribozyme can affect alternative splicing if interposed between an exon and its intronic regulatory elements. This has been demonstrated using two different alternative splicing systems based on alpha-tropomyosin and fibronectin genes. We suggest that there is a requirement for intronic regulatory elements to be covalently attached to exons that are in turn tethered to the elongating polymerase. In the case of the alternatively spliced EDA exon of the fibronectin gene, we demonstrate that the newly identified intronic downstream regulatory element is associated with the splicing regulatory protein SRp20. Our results suggest that targeted hammerhead ribozyme cleavage within introns can be used as a tool to define splicing regulatory elements.
引用
收藏
页码:359 / 366
页数:8
相关论文
共 30 条
[11]   Pre-mRNA splicing and human disease [J].
Faustino, NA ;
Cooper, TA .
GENES & DEVELOPMENT, 2003, 17 (04) :419-437
[12]   The SR splicing factors ASF/SF2 and SC35 have antagonistic effects on intronic enhancer-dependent splicing of the beta-tropomyosin alternative exon 6A [J].
Gallego, ME ;
Gattoni, R ;
Stevenin, J ;
Marie, J ;
ExpertBezancon, A .
EMBO JOURNAL, 1997, 16 (07) :1772-1784
[13]   SMOOTH MUSCLE-SPECIFIC SWITCHING OF ALPHA-TROPOMYOSIN MUTUALLY EXCLUSIVE EXON SELECTION BY SPECIFIC-INHIBITION OF THE STRONG DEFAULT EXON [J].
GOODING, C ;
ROBERTS, GC ;
MOREAU, G ;
NADALGINARD, B ;
SMITH, CWJ .
EMBO JOURNAL, 1994, 13 (16) :3861-3872
[14]  
Gooding C, 1998, RNA, V4, P85
[15]   A splicing silencer that regulates smooth muscle specific alternative splicing is active in multiple cell types [J].
Gromak, N ;
Smith, CWJ .
NUCLEIC ACIDS RESEARCH, 2002, 30 (16) :3548-3557
[16]   Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays [J].
Johnson, JM ;
Castle, J ;
Garrett-Engele, P ;
Kan, ZY ;
Loerch, PM ;
Armour, CD ;
Santos, R ;
Schadt, EE ;
Stoughton, R ;
Shoemaker, DD .
SCIENCE, 2003, 302 (5653) :2141-2144
[17]   Processing of intronic microRNAs [J].
Kim, Young-Kook ;
Kim, V. Narry .
EMBO JOURNAL, 2007, 26 (03) :775-783
[18]   Multiple links between transcription and splicing [J].
Kornblihtt, AR ;
De la Mata, M ;
Fededa, JP ;
Muñoz, MJ ;
Nogués, G .
RNA, 2004, 10 (10) :1489-1498
[19]   An extensive network of coupling among gene expression machines [J].
Maniatis, T ;
Reed, R .
NATURE, 2002, 416 (6880) :499-506
[20]   Understanding alternative splicing: Towards a cellular code [J].
Matlin, AJ ;
Clark, F ;
Smith, CWJ .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (05) :386-398