SnRNP 3768056 216645379 2008-06-02T16:00:28Z 152.121.19.11 text "... so that they can ..." implied intention by a thinking/conscious agent. I replaced said text with indirect verb structure. {{lowercase|title=snRNP}} '''snRNP'''s (pronounced "snurps"), or ''small nuclear ribonucleoproteins'', are particles that combine with [[pre-mRNA]] and various proteins to form [[spliceosome]]s (a type of large molecular complex). SnRNPs "recognize" the places along a strand of [[pre-mRNA]] and are essential in the removal of [[introns]]. These molecules are found within the cell's [[Cell nucleus|nucleus]]. 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]]. These molecules are usually about 150 [[nucleotide]]s long. The snRNA is bound by a [[ribonucleoprotein|Ribonuclear protein]] (RNP) to activate its enzymatic activity. The precise beginnings and ends of [[introns]] on the primary transcripts are marked by signals by which the snRNPs can recognize and remove them. At least four different kinds of snRNPs cooperate in most [[splicing (genetics)|splicing]]. The RNA in these particles is like [[ribosomal RNA]] in that it is used directly, and has both an enzymatic and a structural role. SnRNPs were discovered by [[Michael R. Lerner]] and [[Joan A. Steitz]].<ref>Lerner MR, Steitz, JA, "[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=411675 Antibodies to Small Nuclear RNAs Complexed with Proteins are Produced by Patients with Systemic Lupus Erythematosus]", ''PNAS'' Nov. 1, 1979, v. 76, no. 11, pp. 5495-5499. PMID 316537</ref><ref>Lerner MR, Boyle JA, Mount SM, Wolin SL, Steitz JA, "Are snRNPs involved in splicing?", ''Nature'' Jan. 10, 1980, v. 283, no. 5743, pp. 220-224. PMID 7350545</ref> == Biogenesis == Small nuclear ribonucleoproteins (snRNPs) assemble in a tightly orchestrated and regulated process that involves both the [[cell nucleus]] and [[cytoplasm]].<ref>T. Kiss, "[http://jcs.biologists.org/cgi/content/full/117/25/5949 Biogenesis of small nuclear RNPs]". ''Journal of Cell Science'' (2004) '''117''':5949-5951. PMID 15564372</ref> ===Synthesis and export of RNA in the nucleus=== The [[RNA polymerase II]] transcripts [[U1 snRNA|U1]], [[U2 snRNA|U2]], [[U4 snRNA|U4]], [[U5 snRNA|U5]] and the less abundant [[U11 snRNA|U11]], [[U12 snRNA|U12]] and U4atac ([[Non-coding RNA|snRNAs]]) acquire a m7G-cap which serves as export signal. Nuclear export is mediated by CRM1. ===Synthesis and storage of Sm proteins in the cytoplasm=== The [[LSm|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 B, possibly with D3 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 [[Posttranslational modification|post-translational modification]] in the methylosome.<ref>G. Meister, C. Eggert, D. Buhler, H. Brahms, C. Kambach, U. Fischer, "Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln". ''Current Biology'' (2001) '''11''': 1990-1994. PMID 11747828</ref> These three Sm proteins have repeated [[arginine]]-[[glycine]] motifs in the [[C-terminal end]]s of SmD1, SmD3 and SmB, and the arginine side chains are symmetrically dimethylated to ω-N<sup>G</sup>, N<sup>G'</sup>-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 (protein)|chaperone]], preventing premature assembly of Sm proteins. ===Assembly of core snRNPs in the SMN complex=== The [[Non-coding RNA|snRNAs]] (U1, U2, U4, U5, and the less abundant U11, U12 and U4atac) quickly interact with the '''SMN''' (Survival of Motor Neurons) protein and other proteins ('''Gemins 2-8''') forming the large '''SMN complex'''.<ref>S. Paushkin, A. K. Gubitz, S. Massenet, G. Dreyfuss, "The SMN complex, an assemblyosome of ribonucleoproteins". ''Current Opinion in Cell Biology'' (2002) '''14''': 305-312. {{doi|10.1016/S0955-0674(02)00332-0}} PMID 12067652</ref><ref>J. Yong, L. Wan, G. Dreyfuss, "Why do cells need an assembly machine for RNA-protein complexes?". ''Trends in Cell Biology'' (2004) '''14''':226-232. {{doi|10.1016/j.tcb.2004.03.010}} PMID 15130578</ref> 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 body|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. Nothing is known about this process. ===Defects in snRNP biogenesis as a cause of Spinal muscular atrophy=== Defects in the SMN [[gene]] are associated with premature death of spinal [[motor neuron]]s, and results in [[Spinal muscular atrophy]] (SMA).<ref>P. Selenko, R. Sprangers, G. Stier, D. Buhler, U. Fischer, M. Sattler, "SMN Tudor domain structure and its interaction with the Sm proteins". ''Nature Structural Biology'' (2001) '''8''':27-31. {{doi|10.1038/83014}} PMID 11135666</ref> This [[Genetic disorder|genetic disease]] is manifested over a wide range of severity. The most severe form results in paralysis, is usually fatal by age 2, and is the most common genetic cause of infant death. ==Notes== <references /> ==References== * {{cite book | first=Neil | last=Campbell | coauthors=Reece, Jane | year=2002 | title=Biology | chapter=Chapter 17: From Gene to Protein | edition=6th edition | pages=pg. 312 | publisher=Benjamin Cummings}} * Joan Steitz, April 4, 2006, HHMI Review of SnRNPs, at http://www.hhmi.org/research/investigators/steitzja.html ==External links== * {{MeshName|snRNP}} {{Post transcriptional modification}} [[Category:Molecular biology]]