SnRNP

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.Weaver, Robert F. (2005). Molecular Biology, p.432-448. McGraw-Hill, New York, NY. {{ISBN|0-07-284611-9}}.

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.{{cite journal |vauthors=Montzka KA, Steitz JA | year = 1988 | title = Additional low-abundance human small nuclear ribonucleoproteins: U11, U12, etc | journal = Proc Natl Acad Sci USA | volume = 85 | issue = 23| pages = 8885–8889 | doi = 10.1073/pnas.85.23.8885 | pmid = 2973606 | pmc=282611| bibcode = 1988PNAS...85.8885M | doi-access = free }}

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.{{cite journal |author=Kiss T |title=Biogenesis of small nuclear RNPs |journal=J. Cell Sci. |volume=117 |issue=Pt 25 |pages=5949–51 |date=December 2004 |pmid=15564372 |doi=10.1242/jcs.01487 |doi-access= |s2cid=10316639 }}

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.

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.{{cite journal |vauthors=Meister G, Eggert C, Bühler D, Brahms H, Kambach C, Fischer U |title=Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln |journal=Curr. Biol. |volume=11 |issue=24 |pages=1990–4 |date=December 2001 |pmid=11747828 |doi=10.1016/S0960-9822(01)00592-9|bibcode=2001CBio...11.1990M |hdl=11858/00-001M-0000-0012-F501-7 |s2cid=14742376 |hdl-access=free }} 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-N^G, N^G'-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.

{{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.{{cite journal |author=Paushkin S, Gubitz AK, Massenet S, Dreyfuss G |title=The SMN complex, an assemblyosome of ribonucleoproteins |journal=Curr. Opin. Cell Biol. |volume=14 |issue=3 |pages=305–12 |date=June 2002 |pmid=12067652 |doi=10.1016/S0955-0674(02)00332-0}}{{cite journal |vauthors=Yong J, Wan L, Dreyfuss G |title=Why do cells need an assembly machine for RNA-protein complexes? |journal=Trends Cell Biol. |volume=14 |issue=5 |pages=226–32 |date=May 2004 |pmid=15130578 |doi=10.1016/j.tcb.2004.03.010 }} 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.

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.

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

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.{{Cite journal| doi = 10.1002/wrna.76| pmid = 21957043| title = SMN in spinal muscular atrophy and snRNP biogenesis| journal = Wiley Interdisciplinary Reviews: RNA| volume = 2| issue = 4| pages = 546–564| year = 2011| last1 = Coady | first1 = Tristan H. | last2 = Lorson | first2 = Christian L. | s2cid = 19534375}}

Several human and yeast snRNP structures were determined by the cryo-electron microscopy and successive single particle analysis.

{{Cite journal

| doi = 10.1146/annurev.biophys.35.040405.101953

| pmid = 16689644

| volume = 35

| issue = 1

| pages = 435–457

| last = Stark

| first = Holger

|author2=Reinhard Lührmann

| title = Cryo-Electron Microscopy of Spliceosomal Components

| journal = Annual Review of Biophysics and Biomolecular Structure

| year = 2006

}}

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 parentheses.{{Cite journal

| doi = 10.1038/nature07851

| pmid = 19325628

| issn = 0028-0836

| volume = 458

| issue = 7237

| pages = 475–480

| last = Pomeranz Krummel

| first = Daniel A.

|author2=Chris Oubridge |author3=Adelaine K. W. Leung |author4=Jade Li |author5=Kiyoshi Nagai

| title = Crystal structure of human spliceosomal U1 snRNP at 5.5[thinsp]A resolution

| journal = Nature

| date = 2009-03-26

| pmc = 2673513

}}{{Cite journal

| doi = 10.1038/emboj.2010.295

| issn = 0261-4189

| volume = 29

| issue = 24

| pages = 4172–4184

| last = Weber

| first = Gert

|author2=Simon Trowitzsch |author3=Berthold Kastner |author4=Reinhard Luhrmann |author5=Markus C Wahl

| title = Functional organization of the Sm core in the crystal structure of human U1 snRNP

| journal = EMBO J

| date = 2010-12-15

| pmid=21113136

| pmc=3018796

}}

The structures determined by single particle electron microscopy analysis are: human U1 snRNP,{{Cite journal

| doi = 10.1038/35054102

| issn = 0028-0836

| volume = 409

| issue = 6819

| pages = 539–542

| last = Stark

| first = Holger

|author2=Prakash Dube |author3=Reinhard Luhrmann |author4=Berthold Kastner

| title = Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle

| journal = Nature

| date = 2001-01-25

| pmid=11206553

| bibcode = 2001Natur.409..539S

| s2cid = 4421636

}} human U11/U12 di-snRNP,{{Cite journal

| doi = 10.1016/j.molcel.2005.02.016

| issn = 1097-2765

| volume = 17

| issue = 6

| pages = 869–883

| last = Golas

| first = Monika M.

|author2=Bjoern Sander |author3=Cindy L. Will |author4=Reinhard Lührmann |author5=Holger Stark

| title = Major Conformational Change in the Complex SF3b upon Integration into the Spliceosomal U11/U12 di-snRNP as Revealed by Electron Cryomicroscopy

| journal = Molecular Cell

| date = 2005-03-18

| pmid=15780942

| hdl = 11858/00-001M-0000-0010-93F4-1

| hdl-access = free

}}

human U5 snRNP, U4/U6 di-snRNP, U4/U6∙U5 tri-snRNP.{{Cite journal

| doi = 10.1016/j.molcel.2006.08.021

| issn = 1097-2765

| volume = 24

| issue = 2

| pages = 267–278

| last = Sander

| first = Bjoern

|author2=Monika M. Golas |author3=Evgeny M. Makarov |author4=Hero Brahms |author5=Berthold Kastner |author6=Reinhard Lührmann |author7=Holger Stark

| title = 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

| journal = Molecular Cell

| date = 2006-10-20

| pmid=17052460

| hdl = 11858/00-001M-0000-0010-93DC-C

| hdl-access = free

}}

The further progress determining the structures and functions of snRNPs and spliceosomes continues.{{Cite journal

| doi = 10.1101/cshperspect.a003707

| pmid = 21441581

| volume = 3

| issue = 7

| last = Will

| first = Cindy L.

|author2=Reinhard Lührmann

| title = Spliceosome Structure and Function

| journal = Cold Spring Harbor Perspectives in Biology

| date = 2011-07-01

| page=a003707

| pmc = 3119917

}}

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).

{{reflist|2}}

• [https://www.ibiology.org/genetics-and-gene-regulation/snurps/ Joan Steitz's Short Talk: "SNURPs and Serendipity"]
• {{MeshName|snRNP}}

{{Post transcriptional modification}}

{{Ribonucleoproteins}}

Category:Molecular biology

Category:RNA

Category:Spliceosome

Category:RNA splicing