snRNPs (pronounced "snurps"), or small nuclear ribonucleoproteins, are particles that combine with pre-mRNA and various proteins to form spliceosomes (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 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 nucleotides long. The snRNA is bound by a Ribonuclear protein (RNP) to activate its enzymatic activity.
The precise beginnings and ends of introns on the primary transcripts are marked by signals so that they can be recognized by the snRNPs and removed. At least four different kinds of snRNPs cooperate in most 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.
Synthesis and export of RNA in the nucleus
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 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 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 Neurons) protein and other proteins (Gemins 2-8) forming the large 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. 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 neurons, and results in Spinal muscular atrophy (SMA). This 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.
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