Phylogenetically widespread alternative splicing at unusual GYNGYN donors.
Phylogenetically widespread alternative splicing at unusual GYNGYN donors.
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在不寻常的gyngyn供体上，系统发育广泛的替代剪接。
DOI：
10.1186/gb-2006-7-7-r65
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发表时间：
2006
期刊：
影响因子：
12.3
通讯作者：
Platzer, Matthias
中科院分区：
文献类型：
--
作者：
Hiller, Michael;Huse, Klaus;Szafranski, Karol;Rosenstiel, Philip;Schreiber, Stefan;Backofen, Rolf;Platzer, Matthias
计算和实验证据表明，在一些物种中，不寻常的gyyngyn基序的选择性剪接，在大多数情况下使微妙的蛋白质变异。剪接供体位点具有高度保守的GT或GC二核苷酸和扩展的内含子一致序列GTRAGT，反映了序列与U1 snRNA的互补性。在这里，我们关注的是带有gyyngyn基序的不寻常的供体位点（Y代表C或T； N代表A、C、G或T）。虽然在人类中这些剪接位点中，只有一个GY作为剪接供体起作用，但我们提供了计算和实验证据，表明110个（1.3%）在两个GY供体上都允许选择性剪接。所得到的剪接形式仅在三个核苷酸上不同，这主要导致一个氨基酸的插入/删除。然而，我们也报道了在四种情况下插入停止密码子。在研究选择性剪接与非选择性剪接的gyyngyn供体的区别时，我们发现了与U1 snRNA结合的差异，U1 snRNA结合强度与首选供体之间的强相关性，相邻内含子中序列基序的过度代表，以及人和小鼠之间外显子和内含子侧的更高保守性。将我们的全基因组分析扩展到其他7个真核生物物种，我们发现从小鼠到秀丽隐索线虫，甚至在拟南芥中，所有物种都有选择性剪接的gyyngyn供体。在人类和小鼠中对STAT3基因保守的GTAGTT供体进行实验验证，发现两种物种中选择性剪接转录本的比例非常相似。与一般的选择性剪接相比，除了NAGNAG受体外，gyyngyn供体还能使微妙的蛋白质变异。
Computational and experimental evidence is given for alternative splicing at the unusual GYNGYN motif in several species, enabling in most cases subtle protein variations. Splice donor sites have a highly conserved GT or GC dinucleotide and an extended intronic consensus sequence GTRAGT that reflects the sequence complementarity to the U1 snRNA. Here, we focus on unusual donor sites with the motif GYNGYN (Y stands for C or T; N stands for A, C, G, or T). While only one GY functions as a splice donor for the majority of these splice sites in human, we provide computational and experimental evidence that 110 (1.3%) allow alternative splicing at both GY donors. The resulting splice forms differ in only three nucleotides, which results mostly in the insertion/deletion of one amino acid. However, we also report the insertion of a stop codon in four cases. Investigating what distinguishes alternatively from not alternatively spliced GYNGYN donors, we found differences in the binding to U1 snRNA, a strong correlation between U1 snRNA binding strength and the preferred donor, over-represented sequence motifs in the adjacent introns, and a higher conservation of the exonic and intronic flanks between human and mouse. Extending our genome-wide analysis to seven other eukaryotic species, we found alternatively spliced GYNGYN donors in all species from mouse to Caenorhabditis elegans and even in Arabidopsis thaliana. Experimental verification of a conserved GTAGTT donor of the STAT3 gene in human and mouse reveals a remarkably similar ratio of alternatively spliced transcripts in both species. In contrast to alternative splicing in general, GYNGYN donors in addition to NAGNAG acceptors enable subtle protein variations.