The Caenorhabditis elegans gene mfap-1 encodes a nuclear protein that affects alternative splicing.
The Caenorhabditis elegans gene mfap-1 encodes a nuclear protein that affects alternative splicing.
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秀丽隐杆线虫基因 mfap-1 编码影响选择性剪接的核蛋白
DOI：
10.1371/journal.pgen.1002827
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Horvitz HR
中科院分区：
文献类型：
--
作者：
Ma L;Gao X;Luo J;Huang L;Teng Y;Horvitz HR
RNA剪接是控制真核生物基因表达的主要调控机制。通过从单个前mrna产生各种剪接异构体，选择性剪接在促进后生动物进化复杂性中起着关键作用。已经确定了许多剪接因子。然而，许多剪接因子的体内功能仍有待了解。体内研究对于理解RNA剪接的分子机制和许多RNA剪接相关疾病的生物学至关重要。我们之前从Unc -93（e1500）动物的橡胶带Unc表型抑制基因的遗传筛选中分离出一种秀丽隐杆线虫突变体。该突变体包含秀丽隐杆线虫微纤维相关蛋白1基因mfap-1的两个相邻密码子的错义突变。mfap-1（n4564 n5214）抑制不同橡胶带Unc突变体的Unc表型，其模式类似于剪接因子基因uaf-1（秀丽隐杆线虫U2AF大亚基基因）和sfa-1（秀丽隐杆线虫SF1/BBP基因）的突变。我们使用内源性基因tos-1作为剪接的报告基因，在mfap-1（n4564 n5214）动物中检测到tos-1转录本的内含子1保留和外显子3跳跃增加。利用酵母双杂交筛选，我们分离出剪接因子作为潜在的MFAP-1相互作用物。我们的研究表明秀丽隐杆线虫mfap-1编码一个剪接因子，可以影响选择性剪接。RNA剪接从mrna前转录物中去除中间的内含子序列，并连接相邻的外显子序列以产生功能性信使RNA。许多调节剪接的因子在体内的功能仍有待了解。从由秀丽隐杆线虫Unc -93（e1500）突变引起的橡胶带Unc表型抑制基因的遗传筛选中，我们分离出一个影响高度保守的必需基因mfap-1的突变。MFAP-1是一种广泛表达的核蛋白。MFAP-1可以影响tos-1的选择性剪接，这是一个内源性剪接报告基因，并且是tos-1的一个隐3 '剪接位点剪接改变所必需的。mfap-1增强了uaf-1基因（剪接因子U2AF大亚基）在抑制Unc -93（e1500）动物橡胶带型Unc表型中的作用。我们的研究提供了MFAP-1作为剪接因子的体内证据。
RNA splicing is a major regulatory mechanism for controlling eukaryotic gene expression. By generating various splice isoforms from a single pre–mRNA, alternative splicing plays a key role in promoting the evolving complexity of metazoans. Numerous splicing factors have been identified. However, the in vivo functions of many splicing factors remain to be understood. In vivo studies are essential for understanding the molecular mechanisms of RNA splicing and the biology of numerous RNA splicing-related diseases. We previously isolated a Caenorhabditis elegans mutant defective in an essential gene from a genetic screen for suppressors of the rubberband Unc phenotype of unc-93(e1500) animals. This mutant contains missense mutations in two adjacent codons of the C. elegans microfibrillar-associated protein 1 gene mfap-1. mfap-1(n4564 n5214) suppresses the Unc phenotypes of different rubberband Unc mutants in a pattern similar to that of mutations in the splicing factor genes uaf-1 (the C. elegans U2AF large subunit gene) and sfa-1 (the C. elegans SF1/BBP gene). We used the endogenous gene tos-1 as a reporter for splicing and detected increased intron 1 retention and exon 3 skipping of tos-1 transcripts in mfap-1(n4564 n5214) animals. Using a yeast two-hybrid screen, we isolated splicing factors as potential MFAP-1 interactors. Our studies indicate that C. elegans mfap-1 encodes a splicing factor that can affect alternative splicing. RNA splicing removes intervening intronic sequences from pre–mRNA transcripts and joins adjacent exonic sequences to generate functional messenger RNAs. The in vivo functions of numerous factors that regulate splicing remain to be understood. From a genetic screen for suppressors of the rubberband Unc phenotype caused by the Caenorhabditis elegans unc-93(e1500) mutation, we isolated a mutation that affects a highly conserved essential gene, mfap-1. MFAP-1 is a nuclear protein that is broadly expressed. MFAP-1 can affect the alternative splicing of tos-1, an endogenous reporter gene for splicing, and is required for the altered splicing at a cryptic 3′ splice site of tos-1. mfap-1 enhances the effects of the gene uaf-1 (splicing factor U2AF large subunit) in suppressing the rubberband Unc phenotype of unc-93(e1500) animals. Our studies provide in vivo evidence that MFAP-1 functions as a splicing factor.
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
影响因子：
64.5
作者：
KRAINER, AR;MANIATIS, T
通讯作者：
MANIATIS, T
影响因子：
16
作者：
Blanchette, M;Labourier, E;Rio, DC
通讯作者：
Rio, DC
DOI：
10.1073/pnas.88.21.9578
发表时间：
1991-11-01
影响因子：
11.1
作者：
CHIEN, CT;BARTEL, PL;FIELDS, S
通讯作者：
FIELDS, S
影响因子：
4.8
作者：
Guth, S;Valcárcel, J
通讯作者：
Valcárcel, J