Small nuclear RNA
Small nuclear RNA (snRNA) is a class of
.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 human 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.[2] 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
Classes
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.[3]
The first class, known as Sm-class snRNA, is more widely studied and consists of U1, U2, U4,
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[6] and a 3′ stem–loop, terminating in a stretch of uridines that form the binding site for a distinct heteroheptameric ring of Lsm proteins.[7]
In the spliceosome
Spliceosomes catalyse
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 U12-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.
U1 snRNA
U1 snRNP is the initiator of spliceosomal activity in the cell by base pairing with the 5′ splice site of the pre-mRNA. In the major spliceosome, experimental data has shown that the U1 snRNP is present in equal stoichiometry with U2, U4, U5, and U6 snRNP. However, U1 snRNP's abundance in human cells is far greater than that of the other snRNPs.[14] Through U1 snRNA gene knockdown in HeLa cells, studies have shown the U1 snRNA holds great importance for cellular function. When U1 snRNA genes were knocked out, genomic microarrays showed an increased accumulation of unspliced pre-mRNA.[15] In addition, the knockout was shown to cause premature cleavage and polyadenylation primarily in introns located near the beginning of the transcript. When other uridine based snRNAs were knocked out, this effect was not seen. Thus, U1 snRNA–pre-mRNA base pairing was shown to protect pre-mRNA from polyadenylation as well as premature cleavage. This special protection may explain the overabundance of U1 snRNA in the cell.
snRNPs and human disease
Through the study of small nuclear ribonucleoproteins (snRNPs) and small nucleolar (sno)RNPs we have been able to better understand many important diseases.
Spinal muscular atrophy - Mutations in the survival motor neuron-1 (SMN1) gene result in the degeneration of spinal
Medulloblastoma – The U1 snRNA is mutated in a subset of these brain tumors, and leads to altered RNA splicing.[20] The mutations predominantly occur in adult tumors, and are associated with poor prognosis.
Post-transcriptional modification
In
See also
References
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{{cite book}}
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- ^ (Sarnat HB. Spinal muscular atrophies. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa: Elsevier; 2011:chap 604.2.)
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- ^ (Cooke DW, Divall SA, Radovick S. Normal and aberrant growth. In: Melmed S, ed. Williams Textbook of Endocrinology. 12th ed. Philadelphia: Saunders Elsevier; 2011:chapter 24.)
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External links
- Small+Nuclear+RNA at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Small+Nucleolar+RNA at the U.S. National Library of Medicine Medical Subject Headings (MeSH)