Biomaterial Database

Can donor splice site recognition occur without the involvement of U1 snRNP? 2008

Michela Raponi, and Diana Baralle

Human Genetics Division, University of Southampton, Duthie Building (Mailpoint 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.

Many disease-causing mutations affecting donor splice site recognition are reported in the literature. One of the more frequently observed nucleotide changes causing aberrant splicing are due to mutations in the donor splice site which lower the strength of base pairing with U1 snRNA (small nuclear RNA). However, recent data have highlighted the possibility of a recognition mechanism for weak donor splice sites that are at least partially U1-independent. This is important as most of the donor splice site prediction programs currently in use are based on the U1 snRNA 5'-splice site base pairing and would not pick this up. We review these mechanisms and how an up-to-date donor splice site mutation repertoire indicates the heterogeneity of the molecular mechanism. We suggest that, in clinical molecular genetics, it is important to evaluate sequence variants for aberrant splicing even in those cases where the variant is not thought to alter the U1 snRNA interaction.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D004194	Disease	A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.	Diseases
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012326	RNA Splicing	The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.	RNA, Messenger, Splicing,Splicing, RNA,RNA Splicings,Splicings, RNA
D017412	Ribonucleoprotein, U1 Small Nuclear	A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U1 snRNP along with other small nuclear ribonucleoproteins (U2, U4-U6, and U5) assemble into SPLICEOSOMES that remove introns from pre-mRNA by splicing. The U1 snRNA forms base pairs with conserved sequence motifs at the 5'-splice site and recognizes both the 5'- and 3'-splice sites and may have a fundamental role in aligning the two sites for the splicing reaction.	Small Nuclear Ribonucleoproteins, U1,U1 Small Nuclear Ribonucleoproteins,U1 snRNP,Ribonucleoproteins, Small, U1
D017414	Ribonucleoprotein, U4-U6 Small Nuclear	A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U4-U6 snRNP along with the U5 snRNP preassemble into a single 25S particle that binds to the U1 and U2 snRNPs and the substrate to form mature SPLICEOSOMES. There is also evidence for the existence of individual U4 or U6 snRNPs in addition to their organization as a U4-U6 snRNP.	Ribonucleoproteins, U4 Small Nuclear,Ribonucleoproteins, U6 Small Nuclear,Small Nuclear Ribonucleoproteins, U4,Small Nuclear Ribonucleoproteins, U4-U6,Small Nuclear Ribonucleoproteins, U6,U4 Small Nuclear Ribonucleoproteins,U4 snRNP,U4-U6 Small Nuclear Ribonucleoproteins,U4-U6 snRNP,U6 Small Nuclear Ribonucleoproteins,U6 snRNP,Ribonucleoproteins, Small, U4-U6,Ribonucleoprotein, U4 U6 Small Nuclear,Small Nuclear Ribonucleoproteins, U4 U6,U4 U6 Small Nuclear Ribonucleoproteins
D022821	RNA Splice Sites	Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.	Splice Acceptor Site,Splice Donor Site,3' Splice Site,5' Splice Site,Alternative Splice Sites,Cryptic Splice Sites,3' Splice Sites,5' Splice Sites,Acceptor Site, Splice,Acceptor Sites, Splice,Alternative Splice Site,Cryptic Splice Site,Donor Site, Splice,Donor Sites, Splice,Splice Acceptor Sites,Splice Donor Sites,Splice Site, 3',Splice Site, 5',Splice Site, Alternative,Splice Site, Cryptic,Splice Sites, 3',Splice Sites, 5',Splice Sites, Alternative,Splice Sites, Cryptic