辅助核糖核蛋白组装：SMN和PRMT5复合物在剪接体UsnRNP的形成中协同作用。
Assisted RNP assembly: SMN and PRMT5 complexes cooperate in the formation of spliceosomal UsnRNPs.
作者信息
Meister Gunter, Fischer Utz
机构信息
Max-Planck Institute of Biochemistry, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
出版信息
EMBO J. 2002 Nov 1;21(21):5853-63. doi: 10.1093/emboj/cdf585.
Abstract
Although spliceosomal Sm proteins can assemble spontaneously onto UsnRNA in vitro, this process requires assisting factors in vivo. SMN, the protein involved in spinal muscular atrophy, is part of a complex that contains the Sm proteins and serves as a critical factor for this reaction. Here, we have reconstituted the SMN-dependent assembly of UsnRNPs in vitro. We demonstrate that the SMN complex is necessary and sufficient for the assembly reaction. The PRMT5 complex, previously implicated in methylation and storage of Sm proteins, interacts with the SMN complex and enhances its activity in an ATP-dependent manner. These data uncover the SMN-PRMT5 complex as a functional entity that promotes the assisted assembly of spliceosomal UsnRNPs, and potentially other, RNA-protein complexes.
摘要
尽管剪接体Sm蛋白在体外能够自发地组装到UsnRNA上，但该过程在体内需要辅助因子。与脊髓性肌萎缩症相关的蛋白质SMN是一个包含Sm蛋白的复合物的一部分，并且是此反应的关键因子。在此，我们在体外重建了依赖SMN的UsnRNP组装过程。我们证明，SMN复合物对于组装反应是必需且充分的。先前与Sm蛋白的甲基化和储存有关的PRMT5复合物与SMN复合物相互作用，并以ATP依赖的方式增强其活性。这些数据揭示了SMN-PRMT5复合物是一个功能性实体，它促进剪接体UsnRNP以及可能的其他RNA-蛋白质复合物的辅助组装。
相似文献
1
Assisted RNP assembly: SMN and PRMT5 complexes cooperate in the formation of spliceosomal UsnRNPs.
EMBO J. 2002 Nov 1;21(21):5853-63. doi: 10.1093/emboj/cdf585.
2
Phosphorylation regulates the activity of the SMN complex during assembly of spliceosomal U snRNPs.
EMBO Rep. 2005 Jan;6(1):70-6. doi: 10.1038/sj.embor.7400301.
3
Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins.
Hum Mol Genet. 2000 Aug 12;9(13):1977-86. doi: 10.1093/hmg/9.13.1977.
4
Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy.
Hum Mol Genet. 1999 Dec;8(13):2351-7. doi: 10.1093/hmg/8.13.2351.
5
A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs.
Nat Cell Biol. 2001 Nov;3(11):945-9. doi: 10.1038/ncb1101-945.
6
Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein.
RNA. 2001 Nov;7(11):1531-42. doi: 10.1017/s135583820101442x.
7
An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs.
Cell. 2008 Oct 31;135(3):497-509. doi: 10.1016/j.cell.2008.09.020.
8
The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis.
Cell. 1997 Sep 19;90(6):1023-9. doi: 10.1016/s0092-8674(00)80368-2.
9
Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems.
J Cell Biol. 1999 Dec 13;147(6):1181-94. doi: 10.1083/jcb.147.6.1181.
10
The SMN complex: an assembly machine for RNPs.
Cold Spring Harb Symp Quant Biol. 2006;71:313-20. doi: 10.1101/sqb.2006.71.001.
引用本文的文献
1
Sm-site containing mRNAs can accept Sm-rings and are downregulated in Spinal Muscular Atrophy.
Nucleic Acids Res. 2025 Aug 11;53(15). doi: 10.1093/nar/gkaf794.
2
Emerging roles of protein arginine methyltransferase in multiple myeloma.
Mol Ther Oncol. 2025 May 26;33(2):201003. doi: 10.1016/j.omton.2025.201003. eCollection 2025 Jun 18.
3
Assessment of PRMT6-dependent alternative splicing in pluripotent and differentiating NT2/D1 cells.
Life Sci Alliance. 2025 Feb 3;8(4). doi: 10.26508/lsa.202402946. Print 2025 Apr.
4
Targeting RNA splicing modulation: new perspectives for anticancer strategy?
J Exp Clin Cancer Res. 2025 Jan 30;44(1):32. doi: 10.1186/s13046-025-03279-w.
5
Molecular Characterization and Potential Inhibitors Prediction of Protein Arginine Methyltransferase-2 in Carcinoma: An Insight from Molecular Docking, ADMET Profiling and Molecular Dynamics Simulation Studies.
Euroasian J Hepatogastroenterol. 2024 Jul-Dec;14(2):160-171. doi: 10.5005/jp-journals-10018-1443. Epub 2024 Dec 27.
6
Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.
Signal Transduct Target Ther. 2025 Jan 6;10(1):4. doi: 10.1038/s41392-024-02070-1.
7
PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells.
Oncogene. 2025 Apr;44(13):862-876. doi: 10.1038/s41388-024-03264-1. Epub 2024 Dec 18.
8
R-Methylation in Plants: A Key Regulator of Plant Development and Response to the Environment.
Int J Mol Sci. 2024 Sep 14;25(18):9937. doi: 10.3390/ijms25189937.
9
SART3 reads methylarginine-marked glycine- and arginine-rich motifs.
Cell Rep. 2024 Jul 23;43(7):114459. doi: 10.1016/j.celrep.2024.114459. Epub 2024 Jul 9.
10
A PRMT5-ZNF326 axis mediates innate immune activation upon replication stress.
Sci Adv. 2024 Jun 7;10(23):eadm9589. doi: 10.1126/sciadv.adm9589. Epub 2024 Jun 5.
本文引用的文献
1
SMN-mediated assembly of RNPs: a complex story.
Trends Cell Biol. 2002 Oct;12(10):472-8. doi: 10.1016/s0962-8924(02)02371-1.
2
Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons?
Hum Mol Genet. 2002 Jan 1;11(1):93-105. doi: 10.1093/hmg/11.1.93.
3
Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component.
J Biol Chem. 2002 Mar 1;277(9):7540-5. doi: 10.1074/jbc.M110141200. Epub 2001 Dec 17.
4
Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln.
Curr Biol. 2001 Dec 11;11(24):1990-4. doi: 10.1016/s0960-9822(01)00592-9.
5
Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein.
RNA. 2001 Nov;7(11):1531-42. doi: 10.1017/s135583820101442x.
6
A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs.
Nat Cell Biol. 2001 Nov;3(11):945-9. doi: 10.1038/ncb1101-945.
7
The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins.
Mol Cell Biol. 2001 Dec;21(24):8289-300. doi: 10.1128/MCB.21.24.8289-8300.2001.
8
Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein.
EMBO J. 2001 Oct 1;20(19):5470-9. doi: 10.1093/emboj/20.19.5470.
9
SMN interacts with a novel family of hnRNP and spliceosomal proteins.
EMBO J. 2001 Oct 1;20(19):5443-52. doi: 10.1093/emboj/20.19.5443.
10
Molecular mechanisms in spinal muscular atrophy: models and perspectives.
Curr Opin Neurol. 2001 Oct;14(5):629-34. doi: 10.1097/00019052-200110000-00012.
Zotero 插件