HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition

	HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition
	Heiner, M; Hui, JY; Schreiner, S; Hung, LH; Bindereif, A
刊名	RNA BIOLOGY
	2010
卷号	7 期号:1 页码:56-64
关键词	splicing alternative splicing silencer hnRNP snRNP
通讯作者	Bindereif, A (reprint author), Univ Giessen, Inst Biochem, Giessen, Germany.,albrecht.bindereif@chemie.bio.uni-giessen.de
英文摘要	Heterogeneous nuclear ribonucleoprotein (hnRNP) L can regulate alternative mRNA splicing in diverse ways, binding to exonic or intronic sites and acting as either an activator or repressor. To investigate the mechanistic basis of hnRNP L-regulated alternative splicing, we focus here on two specific cases of hnRNP L-dependent splice site recognition. First, in the case of TJP1 our microarray data had suggested that exon 20 inclusion is regulated by hnRNP L as a repressor. Here we demonstrate by mutational analysis that exon skipping is mediated by a short silencer sequence consisting of three hnRNP L high-score binding motifs located upstream of the 3' splice site of the regulated exon. UV crosslinking and immunoprecipitation experiments showed that hnRNP L binding interferes with 3' splice site recognition by U2AF65. Second, SLC2A2 contains a CA-repeat sequence close to the 5' splice site of the regulated exon 4. Using psoralen crosslinking, we demonstrate that hnRNP L represses splicing by preventing 5' splice site recognition of the U1 snRNP. In sum, our data provide new insights into the mechanisms of how hnRNP L-bound to intronic sites-regulates exon recognition.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TRACT BINDING-PROTEIN ; PRE-MESSENGER-RNA ; POLYPYRIMIDINE TRACT ; CA REPEATS ; PREMESSENGER RNA ; PTB ; EXPRESSION ; REPRESSION ; SEQUENCE ; U2AF
收录类别	SCI
语种	英语
WOS记录号	WOS:000276197800008
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/940]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Heiner, M,Hui, JY,Schreiner, S,et al. HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition[J]. RNA BIOLOGY,2010,7(1):56-64.
APA	Heiner, M,Hui, JY,Schreiner, S,Hung, LH,&Bindereif, A.(2010).HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition.RNA BIOLOGY,7(1),56-64.
MLA	Heiner, M,et al."HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition".RNA BIOLOGY 7.1(2010):56-64.