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snRNP

snRNPs (pronounced "snurps"), or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. The action of snRNPs is essential to the removal of introns from pre-mRNA, a critical aspect of post-transcriptional modification of RNA, occurring only in the nucleus of eukaryotic cells. Additionally, U7 snRNP is not involved in splicing at all, as U7 snRNP is responsible for processing the 3′ stem-loop of histone pre-mRNA.

The two essential components of snRNPs are protein molecules and RNA. The RNA found within each snRNP particle is known as small nuclear RNA, or snRNA, and is usually about 150 nucleotides in length. The snRNA component of the snRNP gives specificity to individual introns by "recognizing" the sequences of critical splicing signals at the 5' and 3' ends and branch site of introns. The snRNA in snRNPs is similar to ribosomal RNA in that it directly incorporates both an enzymatic and a structural role.

SnRNPs were discovered by Michael R. Lerner and Joan A. Steitz.Thomas R. Cech and Sidney Altman also played a role in the discovery, winning the Nobel Prize for Chemistry in 1989 for their independent discoveries that RNA can act as a catalyst in cell development.

Contents

At least five different kinds of snRNPs join the spliceosome to participate in splicing. They can be visualized by gel electrophoresis and are known individually as: U1, U2, U4, U5, and U6. Their snRNA components are known, respectively, as: U1 snRNA, U2 snRNA, U4 snRNA, U5 snRNA, and U6 snRNA.

In the mid-1990s, it was discovered that a variant class of snRNPs exists to help in the splicing of a class of introns found only in metazoans, with highly conserved 5' splice sites and branch sites. This variant class of snRNPs includes: U11 snRNA, U12 snRNA, U4atac snRNA, and U6atac snRNA. While different, they perform the same functions as do U1, U2, U4, and U6, respectively.

Additionally, U7 snRNP is made of U7 small nuclear RNA and associated proteins and is involved in the processing of the 3′ stem-loop of histone pre-mRNA.

Small nuclear ribonucleoproteins (snRNPs) assemble in a tightly orchestrated and regulated process that involves both the cell nucleus and cytoplasm.

Synthesis and export of RNA in the nucleus

The RNA polymerase II transcribes U1, U2, U4, U5 and the less abundant U11, U12 and U4atac (snRNAs) acquire a m7G-cap which serves as an export signal. Nuclear export is mediated by CRM1.

Synthesis and storage of Sm proteins in the cytoplasm

The Sm proteins are synthesized in the cytoplasm by ribosomes translating Sm messenger RNA, just like any other protein. These are stored in the cytoplasm in the form of three partially assembled rings complexes all associated with the pICln protein. They are a 6S pentamer complex of SmD1, SmD2, SmF, SmE and SmG with pICln, a 2-4S complex of SmB, possibly with SmD3 and pICln and the 20S methylosome, which is a large complex of SmD3, SmB, SmD1, pICln and the arginine methyltransferase-5 (PRMT5) protein. SmD3, SmB and SmD1 undergo post-translational modification in the methylosome. These three Sm proteins have repeated arginine-glycine motifs in the C-terminal ends of SmD1, SmD3 and SmB, and the arginine side chains are symmetrically dimethylated to ω-NG, NG'-dimethyl-arginine. It has been suggested that pICln, which occurs in all three precursor complexes but is absent in the mature snRNPs, acts as a specialized chaperone, preventing premature assembly of Sm proteins.

Assembly of core snRNPs in the SMN complex

The snRNAs (U1, U2, U4, U5, and the less abundant U11, U12 and U4atac) quickly interact with the SMN (survival of motor neuron protein); encoded by SMN1 gene) and Gemins 2-8 (Gem-associated proteins: GEMIN2, GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8) forming the SMN complex. It is here that the snRNA binds to the SmD1-SmD2-SmF-SmE-SmG pentamer, followed by addition of the SmD3-SmB dimer to complete the Sm ring around the so-called Sm site of the snRNA. This Sm site is a conserved sequence of nucleotides in these snRNAs, typically AUUUGUGG (where A, U and G represent the nucleosides adenosine, uridine and guanosine, respectively). After assembly of the Sm ring around the snRNA, the 5' terminal nucleoside (already modified to a 7-methylguanosine cap) is hyper-methylated to 2,2,7-trimethylguanosine and the other (3') end of the snRNA is trimmed. This modification, and the presence of a complete Sm ring, is recognized by the snurportin 1 protein.

Final assembly of the snRNPs in the nucleus

The completed core snRNP-snurportin 1 complex is transported into the nucleus via the protein importin β. Inside the nucleus, the core snRNPs appear in the Cajal bodies, where final assembly of the snRNPs take place. This consists of additional proteins and other modifications specific to the particular snRNP (U1, U2, U4, U5). The biogenesis of the U6 snRNP occurs in the nucleus, although large amounts of free U6 are found in the cytoplasm. The LSm ring may assemble first, and then associate with the U6 snRNA.

Disassembly of snRNPs

The snRNPs are very long-lived, but are assumed to be eventually disassembled and degraded. Little is known about the degradation process.

Defective assembly

Defective function of the survival of motor neuron (SMN) protein in snRNP biogenesis, caused by a genetic defect in the SMN1 gene which codes for SMN, may account for the motor neuron pathology observed in the genetic disorder spinal muscular atrophy.

Several human and yeast snRNP structures were determined by the cryo-electron microscopy and successive single particle analysis. Recently, the human U1 snRNP core structure was determined by X-ray crystallography (3CW1, 3PGW), followed by a structure of the U4 core snRNP (2Y9A), which yielded first insights into atomic contacts, especially the binding mode of the Sm proteins to the Sm site. The structure of U6 UsnRNA was solved in complex with a specific protein Prp24 (4N0T), as well as a structure of its 3'-nucleotides bound to the special Lsm2-8 protein ring (4M7A). The PDB codes for the respective structures are mentioned in parenthesis. The structures determined by single particle electron microscopy analysis are: human U1 snRNP, human U11/U12 di-snRNP, human U5 snRNP, U4/U6 di-snRNP, U4/U6∙U5 tri-snRNP. The further progress determining the structures and functions of snRNPs and spliceosomes continues.

Autoantibodies may be produced against the body's own snRNPs, most notably the anti-Sm antibodies targeted against the Sm protein type of snRNP specifically in systemic lupus erythematosus (SLE).

  1. Schümperli, D.; R. S. Pillai (2004-10-01). "The special Sm core structure of the U7 snRNP: far-reaching significance of a small nuclear ribonucleoprotein"(PDF). Cellular and Molecular Life Sciences. 61 (19–20): 2560–2570. doi:10.1007/s00018-004-4190-0. ISSN 1420-682X. PMID 15526162. S2CID 5780814.
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  11. Stark, Holger; Reinhard Lührmann (2006). "Cryo-Electron Microscopy of Spliceosomal Components". Annual Review of Biophysics and Biomolecular Structure. 35 (1): 435–457. doi:10.1146/annurev.biophys.35.040405.101953. PMID 16689644.
  12. Pomeranz Krummel, Daniel A.; Chris Oubridge; Adelaine K. W. Leung; Jade Li; Kiyoshi Nagai (2009-03-26). "Crystal structure of human spliceosomal U1 snRNP at 5.5[thinsp]A resolution". Nature. 458 (7237): 475–480. doi:10.1038/nature07851. ISSN 0028-0836. PMC2673513. PMID 19325628.
  13. Weber, Gert; Simon Trowitzsch; Berthold Kastner; Reinhard Luhrmann; Markus C Wahl (2010-12-15). "Functional organization of the Sm core in the crystal structure of human U1 snRNP". EMBO J. 29 (24): 4172–4184. doi:10.1038/emboj.2010.295. ISSN 0261-4189. PMC3018796. PMID 21113136.
  14. Stark, Holger; Prakash Dube; Reinhard Luhrmann; Berthold Kastner (2001-01-25). "Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle". Nature. 409 (6819): 539–542. Bibcode:2001Natur.409..539S. doi:10.1038/35054102. ISSN 0028-0836. PMID 11206553. S2CID 4421636.
  15. Golas, Monika M.; Bjoern Sander; Cindy L. Will; Reinhard Lührmann; Holger Stark (2005-03-18). "Major Conformational Change in the Complex SF3b upon Integration into the Spliceosomal U11/U12 di-snRNP as Revealed by Electron Cryomicroscopy". Molecular Cell. 17 (6): 869–883. doi:10.1016/j.molcel.2005.02.016. hdl:11858/00-001M-0000-0010-93F4-1. ISSN 1097-2765. PMID 15780942.
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snRNP
snRNP Language Watch Edit snRNPs pronounced snurps or small nuclear ribonucleoproteins are RNA protein complexes that combine with unmodified pre mRNA and various other proteins to form a spliceosome a large RNA protein molecular complex upon which splicing of pre mRNA occurs The action of snRNPs is essential to the removal of introns from pre mRNA a critical aspect of post transcriptional modification of RNA occurring only in the nucleus of eukaryotic cells Additionally U7 snRNP is not involved in splicing at all as U7 snRNP is responsible for processing the 3 stem loop of histone pre mRNA 1 The two essential components of snRNPs are protein molecules and RNA The RNA found within each snRNP particle is known as small nuclear RNA or snRNA and is usually about 150 nucleotides in length The snRNA component of the snRNP gives specificity to individual introns by recognizing the sequences of critical splicing signals at the 5 and 3 ends and branch site of introns The snRNA in snRNPs is similar to ribosomal RNA in that it directly incorporates both an enzymatic and a structural role SnRNPs were discovered by Michael R Lerner and Joan A Steitz 2 3 Thomas R Cech and Sidney Altman also played a role in the discovery winning the Nobel Prize for Chemistry in 1989 for their independent discoveries that RNA can act as a catalyst in cell development Contents 1 Types 2 Biogenesis 2 1 Synthesis and export of RNA in the nucleus 2 2 Synthesis and storage of Sm proteins in the cytoplasm 2 3 Assembly of core snRNPs in the SMN complex 2 4 Final assembly of the snRNPs in the nucleus 2 5 Disassembly of snRNPs 2 6 Defective assembly 3 Structures function and organization 4 Anti snRNP antibodies 5 References 6 External linksTypes EditAt least five different kinds of snRNPs join the spliceosome to participate in splicing They can be visualized by gel electrophoresis and are known individually as U1 U2 U4 U5 and U6 Their snRNA components are known respectively as U1 snRNA U2 snRNA U4 snRNA U5 snRNA and U6 snRNA 4 In the mid 1990s it was discovered that a variant class of snRNPs exists to help in the splicing of a class of introns found only in metazoans with highly conserved 5 splice sites and branch sites This variant class of snRNPs includes U11 snRNA U12 snRNA U4atac snRNA and U6atac snRNA While different they perform the same functions as do U1 U2 U4 and U6 respectively 5 Additionally U7 snRNP is made of U7 small nuclear RNA and associated proteins and is involved in the processing of the 3 stem loop of histone pre mRNA 1 Biogenesis EditSmall nuclear ribonucleoproteins snRNPs assemble in a tightly orchestrated and regulated process that involves both the cell nucleus and cytoplasm 6 Synthesis and export of RNA in the nucleus Edit The RNA polymerase II transcribes U1 U2 U4 U5 and the less abundant U11 U12 and U4atac snRNAs acquire a m7G cap which serves as an export signal Nuclear export is mediated by CRM1 Synthesis and storage of Sm proteins in the cytoplasm Edit The Sm proteins are synthesized in the cytoplasm by ribosomes translating Sm messenger RNA just like any other protein These are stored in the cytoplasm in the form of three partially assembled rings complexes all associated with the pICln protein They are a 6S pentamer complex of SmD1 SmD2 SmF SmE and SmG with pICln a 2 4S complex of SmB possibly with SmD3 and pICln and the 20S methylosome which is a large complex of SmD3 SmB SmD1 pICln and the arginine methyltransferase 5 PRMT5 protein SmD3 SmB and SmD1 undergo post translational modification in the methylosome 7 These three Sm proteins have repeated arginine glycine motifs in the C terminal ends of SmD1 SmD3 and SmB and the arginine side chains are symmetrically dimethylated to w NG NG dimethyl arginine It has been suggested that pICln which occurs in all three precursor complexes but is absent in the mature snRNPs acts as a specialized chaperone preventing premature assembly of Sm proteins Assembly of core snRNPs in the SMN complex Edit See also LSm Gemin6 and Gemin7 The snRNAs U1 U2 U4 U5 and the less abundant U11 U12 and U4atac quickly interact with the SMN survival of motor neuron protein encoded by SMN1 gene and Gemins 2 8 Gem associated proteins GEMIN2 GEMIN3 GEMIN4 GEMIN5 GEMIN6 GEMIN7 GEMIN8 forming the SMN complex 8 9 It is here that the snRNA binds to the SmD1 SmD2 SmF SmE SmG pentamer followed by addition of the SmD3 SmB dimer to complete the Sm ring around the so called Sm site of the snRNA This Sm site is a conserved sequence of nucleotides in these snRNAs typically AUUUGUGG where A U and G represent the nucleosides adenosine uridine and guanosine respectively After assembly of the Sm ring around the snRNA the 5 terminal nucleoside already modified to a 7 methylguanosine cap is hyper methylated to 2 2 7 trimethylguanosine and the other 3 end of the snRNA is trimmed This modification and the presence of a complete Sm ring is recognized by the snurportin 1 protein Final assembly of the snRNPs in the nucleus Edit The completed core snRNP snurportin 1 complex is transported into the nucleus via the protein importin b Inside the nucleus the core snRNPs appear in the Cajal bodies where final assembly of the snRNPs take place This consists of additional proteins and other modifications specific to the particular snRNP U1 U2 U4 U5 The biogenesis of the U6 snRNP occurs in the nucleus although large amounts of free U6 are found in the cytoplasm The LSm ring may assemble first and then associate with the U6 snRNA Disassembly of snRNPs Edit The snRNPs are very long lived but are assumed to be eventually disassembled and degraded Little is known about the degradation process Defective assembly Edit Defective function of the survival of motor neuron SMN protein in snRNP biogenesis caused by a genetic defect in the SMN1 gene which codes for SMN may account for the motor neuron pathology observed in the genetic disorder spinal muscular atrophy 10 Structures function and organization EditSeveral human and yeast snRNP structures were determined by the cryo electron microscopy and successive single particle analysis 11 Recently the human U1 snRNP core structure was determined by X ray crystallography 3CW1 3PGW followed by a structure of the U4 core snRNP 2Y9A which yielded first insights into atomic contacts especially the binding mode of the Sm proteins to the Sm site The structure of U6 UsnRNA was solved in complex with a specific protein Prp24 4N0T as well as a structure of its 3 nucleotides bound to the special Lsm2 8 protein ring 4M7A The PDB codes for the respective structures are mentioned in parenthesis 12 13 The structures determined by single particle electron microscopy analysis are human U1 snRNP 14 human U11 U12 di snRNP 15 human U5 snRNP U4 U6 di snRNP U4 U6 U5 tri snRNP 16 The further progress determining the structures and functions of snRNPs and spliceosomes continues 17 Anti snRNP antibodies EditAutoantibodies may be produced against the body s own snRNPs most notably the anti Sm antibodies targeted against the Sm protein type of snRNP specifically in systemic lupus erythematosus SLE References Edit a b Schumperli D R S Pillai 2004 10 01 The special Sm core structure of the U7 snRNP far reaching significance of a small nuclear ribonucleoprotein PDF Cellular and Molecular Life Sciences 61 19 20 2560 2570 doi 10 1007 s00018 004 4190 0 ISSN 1420 682X PMID 15526162 S2CID 5780814 Lerner MR Steitz JA November 1979 Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus Proc Natl Acad Sci U S A 76 11 5495 9 Bibcode 1979PNAS 76 5495R doi 10 1073 pnas 76 11 5495 PMC 411675 PMID 316537 Lerner MR Boyle JA Mount SM Wolin SL Steitz JA January 1980 Are snRNPs involved in splicing Nature 283 5743 220 4 Bibcode 1980Natur 283 220L doi 10 1038 283220a0 PMID 7350545 S2CID 4266714 Weaver Robert F 2005 Molecular Biology p 432 448 McGraw Hill New York NY ISBN 0 07 284611 9 Montzka KA Steitz JA 1988 Additional low abundance human small nuclear ribonucleoproteins U11 U12 etc Proc Natl Acad Sci USA 85 23 8885 8889 Bibcode 1988PNAS 85 8885M doi 10 1073 pnas 85 23 8885 PMC 282611 PMID 2973606 Kiss T December 2004 Biogenesis of small nuclear RNPs J Cell Sci 117 Pt 25 5949 51 doi 10 1242 jcs 01487 PMID 15564372 Meister G Eggert C Buhler D Brahms H Kambach C Fischer U December 2001 Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln Curr Biol 11 24 1990 4 doi 10 1016 S0960 9822 01 00592 9 hdl 11858 00 001M 0000 0012 F501 7 PMID 11747828 S2CID 14742376 Paushkin S Gubitz AK Massenet S Dreyfuss G June 2002 The SMN complex an assemblyosome of ribonucleoproteins Curr Opin Cell Biol 14 3 305 12 doi 10 1016 S0955 0674 02 00332 0 PMID 12067652 CS1 maint multiple names authors list link Yong J Wan L Dreyfuss G May 2004 Why do cells need an assembly machine for RNA protein complexes Trends Cell Biol 14 5 226 32 doi 10 1016 j tcb 2004 03 010 PMID 15130578 Coady Tristan H Lorson Christian L 2011 SMN in spinal muscular atrophy and snRNP biogenesis Wiley Interdisciplinary Reviews RNA 2 4 546 564 doi 10 1002 wrna 76 PMID 21957043 S2CID 19534375 Stark Holger Reinhard Luhrmann 2006 Cryo Electron Microscopy of Spliceosomal Components Annual Review of Biophysics and Biomolecular Structure 35 1 435 457 doi 10 1146 annurev biophys 35 040405 101953 PMID 16689644 Pomeranz Krummel Daniel A Chris Oubridge Adelaine K W Leung Jade Li Kiyoshi Nagai 2009 03 26 Crystal structure of human spliceosomal U1 snRNP at 5 5 thinsp A resolution Nature 458 7237 475 480 doi 10 1038 nature07851 ISSN 0028 0836 PMC 2673513 PMID 19325628 Weber Gert Simon Trowitzsch Berthold Kastner Reinhard Luhrmann Markus C Wahl 2010 12 15 Functional organization of the Sm core in the crystal structure of human U1 snRNP EMBO J 29 24 4172 4184 doi 10 1038 emboj 2010 295 ISSN 0261 4189 PMC 3018796 PMID 21113136 Stark Holger Prakash Dube Reinhard Luhrmann Berthold Kastner 2001 01 25 Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle Nature 409 6819 539 542 Bibcode 2001Natur 409 539S doi 10 1038 35054102 ISSN 0028 0836 PMID 11206553 S2CID 4421636 Golas Monika M Bjoern Sander Cindy L Will Reinhard Luhrmann Holger Stark 2005 03 18 Major Conformational Change in the Complex SF3b upon Integration into the Spliceosomal U11 U12 di snRNP as Revealed by Electron Cryomicroscopy Molecular Cell 17 6 869 883 doi 10 1016 j molcel 2005 02 016 hdl 11858 00 001M 0000 0010 93F4 1 ISSN 1097 2765 PMID 15780942 Sander Bjoern Monika M Golas Evgeny M Makarov Hero Brahms Berthold Kastner Reinhard Luhrmann Holger Stark 2006 10 20 Organization of Core Spliceosomal Components U5 snRNA Loop I and U4 U6 Di snRNP within U4 U6 U5 Tri snRNP as Revealed by Electron Cryomicroscopy Molecular Cell 24 2 267 278 doi 10 1016 j molcel 2006 08 021 hdl 11858 00 001M 0000 0010 93DC C ISSN 1097 2765 PMID 17052460 Will Cindy L Reinhard Luhrmann 2011 07 01 Spliceosome Structure and Function Cold Spring Harbor Perspectives in Biology 3 7 a003707 doi 10 1101 cshperspect a003707 PMC 3119917 PMID 21441581 External links EditJoan Steitz s Short Talk SNURPs and Serendipity snRNP at the US National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title SnRNP amp oldid 1045343262, wikipedia, wiki, book,

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