A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System.
A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System.
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DOI：
10.3390/cells9112340
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发表时间：
2020-10-22
期刊：
影响因子：
6
通讯作者：
Taylor MR
中科院分区：
文献类型：
--
作者：
Henson HE;Taylor MR
剪接体由辅助蛋白和从RNA中去除内含子的小核核糖核蛋白（snRNP）组成。由于剪接缺陷与退行性疾病有关，因此更好地了解剪接体的形成和功能至关重要。我们提供了一个剪接体蛋白U4/U6.U5三snRNP相关蛋白1，或鳞状细胞癌抗原识别的T细胞（Sart 1）的作用的见解。Sart 1将U4.U6/U 5三-snRNP复合物募集到核RNA。然后复合物与U1和U2 snRNP结合形成剪接体。正向遗传筛选识别脉络丛发育缺陷和全外显子组测序（WES）确定了斑马鱼sart 1外显子12的点突变。该突变导致sart 1的上调。使用RNA-Seq分析，我们确定了额外的上调基因，包括参与细胞凋亡的基因。我们还观察到大脑和眼睛中激活的caspase 3增加，视觉相关基因下调。尽管剪接发生在许多细胞类型中，但斑马鱼中的sart 1表达仅限于大脑。通过确定sart 1在大脑中的表达和中枢神经系统（CNS）内的细胞死亡，我们提供了更多的见解sart 1在特定组织中的作用。我们还描述了sart 1参与细胞死亡和视觉相关通路的特征。
The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.
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影响因子：
--
作者：
Thambisetty, Madhav;Simmons, Andrew;Velayudhan, Latha;Hye, Abdul;Campbell, James;Zhang, Yi;Wahlund, Lars-Olof;Westman, Eric;Kinsey, Anna;Guntert, Andreas;Proitsi, Petroula;Powell, John;Causevic, Mirsada;Killick, Richard;Lunnon, Katie;Lynham, Steven;Broadstock, Martin;Choudhry, Fahd;Howlett, David R.;Williams, Robert J.;Sharp, Sally I.;Mitchelmore, Cathy;Tunnard, Catherine;Leung, Rufina;Foy, Catherine;O'Brien, Darragh;Breen, Gerome;Furney, Simon J.;Ward, Malcolm;Kloszewska, Iwona;Mecocci, Patrizia;Soininen, Hilkka;Tsolaki, Magda;Vellas, Bruno;Hodges, Angela;Murphy, Declan G. M.;Parkins, Sue;Richardson, Jill C.;Resnick, Susan M.;Ferrucci, Luigi;Wong, Dean F.;Zhou, Yun;Muehlboeck, Sebastian;Evans, Alan;Francis, Paul T.;Spenger, Christian;Lovestone, Simon
通讯作者：
Lovestone, Simon
影响因子：
5.7
作者：
Allen WL;Stevenson L;Coyle VM;Jithesh PV;Proutski I;Carson G;Gordon MA;Lenz HJ;Van Schaeybroeck S;Longley DB;Johnston PG
通讯作者：
Johnston PG
影响因子：
2.6
作者：
Rozovski U;Keating M;Estrov Z
通讯作者：
Estrov Z
影响因子：
4.8
作者：
Leskov, KS;Klokov, DY;Boothman, DA
通讯作者：
Boothman, DA
影响因子：
4.3
作者：
Henson, Hannah E.;Parupalli, Chaithanyarani;Taylor, Michael R.
通讯作者：
Taylor, Michael R.