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激酶 DYRKIA 通过磷酸化剪接体成分 SAP155 来调节精原细胞中的前体 mRNA 剪接以及精原细胞和支持细胞的增殖,这一过程发生在出生后小鼠的睾丸中。

The kinase DYRKIA regulates pre-mRNA splicing in spermatogonia and proliferation of spermatogonia and Sertoli cells by phosphorylating a spliceosomal component, SAP155, in postnatal murine testes.

机构信息

Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan.

出版信息

Mol Cell Biochem. 2011 Sep;355(1-2):217-22. doi: 10.1007/s11010-011-0857-7. Epub 2011 May 8.

DOI:10.1007/s11010-011-0857-7
PMID:21553260
Abstract

SAP155 is an essential component of the spliceosome and its phosphorylation is required for splicing catalysis, but little is known concerning its function and regulation during spermatogenesis in postnatal murine testes. We report that inhibition of dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) IA strongly suppressed the mitogen-stimulated SAP155 phosphorylation and constitutive splicing of IκB pre-mRNA as well as the proliferation of spermatogonial and Sertoli cells in cultures of the 6-day post partum testes and a spermatogonial cell line, but not in a Sertoli cell line. Our findings suggest that the active spliceosome, containing SAP155 phosphorylated by DYRKIA, performs pre-mRNA splicing in spermatogonia during testicular development.

摘要

SAP155 是剪接体的必需组成部分,其磷酸化对于剪接催化是必需的,但对于其在出生后小鼠睾丸中的精子发生过程中的功能和调节知之甚少。我们报告称,双重特异性酪氨酸磷酸化调节激酶(DYRK)IA 的抑制强烈抑制了有丝分裂原刺激的 SAP155 磷酸化和 IκB 前体 mRNA 的组成性剪接,以及产后 6 天睾丸和精原细胞系中精原细胞和支持细胞的增殖,但在支持细胞系中没有。我们的发现表明,含有 DYRKIA 磷酸化的 SAP155 的活性剪接体在睾丸发育过程中的精原细胞中进行前体 mRNA 剪接。

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The kinase DYRKIA regulates pre-mRNA splicing in spermatogonia and proliferation of spermatogonia and Sertoli cells by phosphorylating a spliceosomal component, SAP155, in postnatal murine testes.激酶 DYRKIA 通过磷酸化剪接体成分 SAP155 来调节精原细胞中的前体 mRNA 剪接以及精原细胞和支持细胞的增殖,这一过程发生在出生后小鼠的睾丸中。
Mol Cell Biochem. 2011 Sep;355(1-2):217-22. doi: 10.1007/s11010-011-0857-7. Epub 2011 May 8.
2
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本文引用的文献

1
Phosphorylated SAP155, the spliceosomal component, is localized to chromatin in postnatal mouse testes.磷酸化 SAP155,剪接体成分,定位于出生后小鼠睾丸的染色质中。
Biochem Biophys Res Commun. 2010 Mar 19;393(4):577-81. doi: 10.1016/j.bbrc.2010.02.014. Epub 2010 Feb 12.
2
Reduced expression of an RNA-binding protein by prolactin leads to translational silencing of programmed cell death protein 4 and apoptosis in newt spermatogonia.催乳素导致RNA结合蛋白表达降低,进而使蝾螈精原细胞中的程序性细胞死亡蛋白4发生翻译沉默并引发细胞凋亡。
J Biol Chem. 2009 Aug 28;284(35):23260-71. doi: 10.1074/jbc.M109.018622. Epub 2009 Jun 25.
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综合蛋白质组学和磷酸化蛋白质组学分析鉴定的沼泽水牛(Bubalus bubalis)精子发生中的新靶标。
Sci Rep. 2020 Sep 24;10(1):15659. doi: 10.1038/s41598-020-72353-4.
4
Splicing Factor 3B Subunit 1 Interacts with HIV Tat and Plays a Role in Viral Transcription and Reactivation from Latency.剪接因子 3B 亚基 1 与 HIV Tat 相互作用,并在潜伏病毒转录和激活中发挥作用。
mBio. 2018 Nov 6;9(6):e01423-18. doi: 10.1128/mBio.01423-18.
5
Glycogen synthase kinase-3 and alternative splicing.糖原合成酶激酶-3 和选择性剪接。
Wiley Interdiscip Rev RNA. 2018 Nov;9(6):e1501. doi: 10.1002/wrna.1501. Epub 2018 Aug 17.
6
Cyclin-dependent kinase 1 (CDK1) and CDK2 have opposing roles in regulating interactions of splicing factor 3B1 with chromatin.细胞周期蛋白依赖性激酶 1(CDK1)和 CDK2 在调节剪接因子 3B1 与染色质相互作用方面具有相反的作用。
J Biol Chem. 2018 Jun 29;293(26):10220-10234. doi: 10.1074/jbc.RA118.001654. Epub 2018 May 15.
7
Melanoma Differentiation-associated Gene 7/IL-24 Exerts Cytotoxic Effects by Altering the Alternative Splicing of Bcl-x Pre-mRNA via the SRC/PKCδ Signaling Axis.黑色素瘤分化相关基因7/白细胞介素-24通过SRC/PKCδ信号轴改变Bcl-x前体mRNA的可变剪接发挥细胞毒性作用。
J Biol Chem. 2016 Oct 7;291(41):21669-21681. doi: 10.1074/jbc.M116.737569. Epub 2016 Aug 12.
8
Major spliceosome defects cause male infertility and are associated with nonobstructive azoospermia in humans.主要剪接体缺陷会导致男性不育,并且与人类非梗阻性无精子症相关。
Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4134-9. doi: 10.1073/pnas.1513682113. Epub 2016 Mar 28.
Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA.
剪接抑制素A作用于剪接因子3b(SF3b),并抑制前体信使核糖核酸(pre-mRNA)的剪接和核滞留。
Nat Chem Biol. 2007 Sep;3(9):576-83. doi: 10.1038/nchembio.2007.18. Epub 2007 Jul 22.
4
NSSR1 is regulated in testes development and cryptorchidism and promotes the exon 5-included splicing of CREB transcripts.NSSR1在睾丸发育和隐睾症中受到调控,并促进包含CREB转录本外显子5的剪接。
Mol Reprod Dev. 2007 Nov;74(11):1363-72. doi: 10.1002/mrd.20719.
5
The expression of the testis-specific Dyrk4 kinase is highly restricted to step 8 spermatids but is not required for male fertility in mice.睾丸特异性Dyrk4激酶的表达高度局限于第8期精子细胞,但对小鼠雄性生育力并非必需。
Mol Cell Endocrinol. 2007 Mar 15;267(1-2):80-8. doi: 10.1016/j.mce.2006.12.041. Epub 2007 Jan 17.
6
The protein kinase DYRK1A phosphorylates the splicing factor SF3b1/SAP155 at Thr434, a novel in vivo phosphorylation site.蛋白激酶DYRK1A在苏氨酸434位点使剪接因子SF3b1/SAP155磷酸化,这是一个新发现的体内磷酸化位点。
BMC Biochem. 2006 Mar 2;7:7. doi: 10.1186/1471-2091-7-7.
7
Spermatogonial cell-mediated activation of an IkappaBzeta-independent nuclear factor-kappaB pathway in Sertoli cells induces transcription of the lipocalin-2 gene.精原细胞介导的支持细胞中不依赖IκBζ的核因子κB信号通路激活可诱导脂质运载蛋白-2基因转录。
Mol Endocrinol. 2006 Apr;20(4):904-15. doi: 10.1210/me.2005-0423. Epub 2005 Dec 1.
8
TESSP-1: a novel serine protease gene expressed in the spermatogonia and spermatocytes of adult mouse testes.TESSP-1:一个在成年小鼠睾丸的精原细胞和精母细胞中表达的新型丝氨酸蛋白酶基因。
Mol Reprod Dev. 2005 Jan;70(1):1-10. doi: 10.1002/mrd.20184.
9
Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and colocalization with splicing factors.细胞周期蛋白L2的特性:一种具有富含精氨酸/丝氨酸结构域的新型细胞周期蛋白,受DYRK1A磷酸化并与剪接因子共定位
J Biol Chem. 2004 Feb 6;279(6):4612-24. doi: 10.1074/jbc.M310794200. Epub 2003 Nov 17.
10
Alternative splicing in the testes.睾丸中的可变剪接。
Curr Opin Genet Dev. 2002 Oct;12(5):615-19. doi: 10.1016/s0959-437x(02)00347-7.