Small nuclear RNA

snRNA are always associated with a set of specific proteins, and the complexes are referred to as small nuclear ribonucleoproteins (snRNP, often pronounced 'snurps'). Each snRNP particle is composed of a snRNA component and several snRNP-specific proteins (including Sm proteins, a family of nuclear proteins). The most common snRNA components of these complexes are known, respectively, as: U1 spliceosomal RNA, U2 spliceosomal RNA, U4 spliceosomal RNA, U5 spliceosomal RNA, and U6 spliceosomal RNA. Their nomenclature derives from their high uridine content. snRNAs were discovered by accident during a gel electrophoresis experiment in 1966. An unexpected type of RNA was found in the gel and investigated. Later analysis has shown that these RNA were high in uridylate and were established in the nucleus. snRNAs and small nucleolar RNAs (snoRNAs) are not the same and is not a type of one another. Both are different and are a class under small RNAs. These are small RNA molecules that play an essential role in RNA biogenesis and guide chemical modifications of ribosomal RNAs (rRNAs) and other RNA genes (tRNA and snRNAs). They are located in the nucleolus and the Cajal bodies of eukaryotic cells (the major sites of RNA synthesis), where they are called scaRNAs (small Cajal body-specific RNAs). snRNA are often divided into two classes based upon both common sequence features as well as associated protein factors such as the RNA-binding LSm proteins. The first class, known as Sm-class snRNA, is more widely studied and consists of U1, U2, U4, U4atac, U5, U7, U11, and U12. Sm-class snRNA are transcribed by RNA polymerase II. The pre-snRNA are transcribed and receive the usual 7-methylguanosine five-prime cap in the nucleus. They are then exported to the cytoplasm through nuclear pores for further processing. In the cytoplasm, the snRNA receive 3' trimming to form a 3' stem-loop structure, as well as hypermethylation of the 5' cap to form trimethylguanosine. The 3' stem structure is necessary for recognition by the survival of motor neuron (SMN) protein. This complex assembles the snRNA into stable ribonucleoproteins (RNPs). The modified 5' cap is then required to import the snRNP back into the nucleus. All of these uridine-rich snRNA, with the exception of U7, form the core of the spliceosome. Splicing, or the removal of introns, is a major aspect of post-transcriptional modification, and takes place only in the nucleus of eukaryotes. U7 snRNA has been found to function in histone pre-mRNA processing. The second class, known as Lsm-class snRNA, consists of U6 and U6atac. Lsm-class snRNAs are transcribed by RNA polymerase III and never leave the nucleus, in contrast to Sm-class snRNA. Lsm-class snRNAs contain a 5'-γ-monomethylphosphate cap and a 3' stem–loop, terminating in a stretch of uridines that form the binding site for a distinct heteroheptameric ring of Lsm proteins. Spliceosomes catalyse splicing, an integral step in eukaryotic precursor messenger RNA maturation. A splicing mistake in even a single nucleotide can be devastating to the cell, and a reliable, repeatable method of RNA processing is necessary to ensure cell survival. The spliceosome is a large, protein-RNA complex that consists of five small nuclear RNAs (U1, U2, U4, U5, and U6) and over 150 proteins. The snRNAs, along with their associated proteins, form ribonucleoprotein complexes (snRNPs), which bind to specific sequences on the pre-mRNA substrate. This intricate process results in two sequential transesterification reactions. These reactions will produce a free lariat intron and ligate two exons to form a mature mRNA. There are two separate classes of spliceosomes. The major class, which is far more abundant in eukaryotic cells, splices primarily U2-type introns. The initial step of splicing is the bonding of the U1 snRNP and its associated proteins to the 5’ splice end to the hnRNA. This creates the commitment complex which will constrain the hnRNA to the splicing pathway. Then, U2 snRNP is recruited to the spliceosome binding site and forms complex A, after which the U5.U4/U6 tri-snRNP complex binds to complex A to form the structure known as complex B. After rearrangement, complex C is formed, and the spliceosome is active for catalysis. In the catalytically active spliceosome U2 and U6 snRNAs fold to form a conserved structure called the catalytic triplex. This structure coordinates two magnesium ions that form the active site of the spliceosome. This is an example of RNA catalysis. In addition to this main spliceosome complex, there exists a much less common (~1%) minor spliceosome. This complex comprises U11, U12, U4atac, U6atac and U5 snRNPs. These snRNPs are functional analogs of the snRNPs used in the major spliceosome. The minor spliceosome splices U-12 type introns. The two types of introns mainly differ in their splicing sites: U2-type introns have GT-AG 5' and 3' splice sites while U12-type introns have AT-AC at their 5' and 3' ends. The minor spliceosome carries out its function through a different pathway from the major spliceosome.