Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts
Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts
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DOI：
10.1101/gr.082503.108
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发表时间：
2009-03-01
期刊：
影响因子：
7
通讯作者：
Liu, Yunlong
中科院分区：
文献类型：
--
作者：
Sanford, Jeremy R.;Wang, Xin;Liu, Yunlong
后生动物的基因至少有两个叠加的密码进行加密：遗传密码，以指定蛋白质的一级结构和剪接代码，以扩大其蛋白质组输出通过选择性剪接。在这里，我们定义了一个中央调节器的特异性前mRNA剪接，保守的，必不可少的剪接因子SFRS 1。交联免疫沉淀和高通量测序（CLIP-seq）在培养的人胚肾细胞的转录组中鉴定了23，632个SFRS 1结合位点。SFRS 1被发现参与许多不同类别的功能不同的转录本，包括mRNA，miRNA，snoRNA，ncRNA和保守的基因间转录本的未知功能。这些不同的成绩单大多数共享一个富含嘌呤的共识基序对应的典型SFRS 1结合位点。共识网站不仅丰富的外显子交联SFRS 1在体内，但也丰富的剪接位点附近。编码RNA加工因子的mRNA显著过量，表明SFRS 1可能广泛影响体内基因表达的转录后控制。最后，在人类基因突变数据库中搜索SFRS 1共有基序，在82个不同的基因中发现了181个突变，这些突变破坏了预测的SFRS 1结合位点。这种全面的分析大大扩展了已知的作用，人类SR蛋白质的调节多种多样的RNA转录本。
Metazoan genes are encrypted with at least two superimposed codes: the genetic code to specify the primary structure of proteins and the splicing code to expand their proteomic output via alternative splicing. Here, we define the specificity of a central regulator of pre-mRNA splicing, the conserved, essential splicing factor SFRS1. Cross-linking immunoprecipitation and high-throughput sequencing (CLIP-seq) identified 23,632 binding sites for SFRS1 in the transcriptome of cultured human embryonic kidney cells. SFRS1 was found to engage many different classes of functionally distinct transcripts including mRNA, miRNA, snoRNAs, ncRNAs, and conserved intergenic transcripts of unknown function. The majority of these diverse transcripts share a purine-rich consensus motif corresponding to the canonical SFRS1 binding site. The consensus site was not only enriched in exons cross-linked to SFRS1 in vivo, but was also enriched in close proximity to splice sites. mRNAs encoding RNA processing factors were significantly overrepresented, suggesting that SFRS1 may broadly influence the post-transcriptional control of gene expression in vivo. Finally, a search for the SFRS1 consensus motif within the Human Gene Mutation Database identified 181 mutations in 82 different genes that disrupt predicted SFRS1 binding sites. This comprehensive analysis substantially expands the known roles of human SR proteins in the regulation of a diverse array of RNA transcripts.