Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements

被引:480
作者
Lareau, Liana F.
Inada, Maki
Green, Richard E.
Wengrod, Jordan C.
Brenner, Steven E. [1 ]
机构
[1] Univ Calif Berkeley, Dept Cell & Mol Biol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
D O I
10.1038/nature05676
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The human and mouse genomes share a number of long, perfectly conserved nucleotide sequences, termed ultraconserved elements(1). Whereas these regions can act as transcriptional enhancers when upstream of genes, those within genes are less well understood. In particular, the function of ultraconserved elements that overlap alternatively spliced exons of genes encoding RNA-binding proteins is unknown(1,2). Here we report that in every member of the human SR family of splicing regulators, highly or ultraconserved elements are alternatively spliced, either as alternative 'poison cassette exons' containing early in-frame stop codons, or as alternative introns in the 3' untranslated region. These alternative splicing events target the resulting messenger RNAs for degradation by means of an RNA surveillance pathway called nonsense-mediated mRNA decay. Mouse orthologues of the human SR proteins exhibit the same unproductive splicing patterns. Three SR proteins have been previously shown to direct splicing of their own transcripts, and one of these is known to autoregulate its expression by coupling alternative splicing with decay(3-5); our results suggest that unproductive splicing is important for regulation of the entire SR family. We find that unproductive splicing associated with conserved regions has arisen independently in different SR genes, suggesting that splicing factors may readily acquire this form of regulation.
引用
收藏
页码:926 / 929
页数:4
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