Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene. [5]
Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene. [5]
In eukaryotes, the introns in the transcribed pre-mRNA first have to be removed by spliceosome in order to form a mature mRNA. A spliceosome is assembled from small nuclear ribonucleoproteins(snRNP) and small nuclear RNAs(snRNA). And the splicing factor can be divided into snRNP and non snRNP proteins.U2 auxiliary factor (U2AF), composed of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit, which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple alternatively spliced transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date. [6]
In humans and other tetrapods, it has been shown that without U2AF2, the splicing process is inhibited. However, in zebrafish and other teleosts the RNA splicing process can still occur on certain genes in the absence of U2AF2. This may be because 10% of genes have alternating TG and AC base pairs at the 3' splice site (3'ss) and 5' splice site (5'ss) respectively on each intron, which alters the secondary structure of the RNA and influences splicing. [7]
The splicing factor U2AF65 can specifically recognizes the polypyrimidine tract (Py tract), that’s because U2AF65 consists of 3 RNA binding domains (RRMs), all of them have a high binding affinity to the Py tract on its adjacent 3’ splice site. [6] The RRM1 and RRM2 are sufficient for specific RNA/protein binding, while RRM3 is responsible for protein/protein interactions. For example, the C-Terminal RRM3 contribute to establish protein–protein contacts with splicing factors like UAP56, SAP155, and mBBP/SF1. [8]
U2AF2 has been shown to interact with:
RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns and splicing back together exons. For nuclear-encoded genes, splicing occurs in the nucleus either during or immediately after transcription. For those eukaryotic genes that contain introns, splicing is usually needed to create an mRNA molecule that can be translated into protein. For many eukaryotic introns, splicing occurs in a series of reactions which are catalyzed by the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs). There exist self-splicing introns, that is, ribozymes that can catalyze their own excision from their parent RNA molecule. The process of transcription, splicing and translation is called gene expression, the central dogma of molecular biology.
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specific proteins to form a small nuclear ribonucleoprotein complex, which in turn combines with other snRNPs to form a large ribonucleoprotein complex called a spliceosome. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. An analogy is a film editor, who selectively cuts out irrelevant or incorrect material from the initial film and sends the cleaned-up version to the director for the final cut.
SR proteins are a conserved family of proteins involved in RNA splicing. SR proteins are named because they contain a protein domain with long repeats of serine and arginine amino acid residues, whose standard abbreviations are "S" and "R" respectively. SR proteins are ~200-600 amino acids in length and composed of two domains, the RNA recognition motif (RRM) region and the RS domain. SR proteins are more commonly found in the nucleus than the cytoplasm, but several SR proteins are known to shuttle between the nucleus and the cytoplasm.
Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcribed by either RNA polymerase II or RNA polymerase III. Their primary function is in the processing of pre-messenger RNA (hnRNA) in the nucleus. They have also been shown to aid in the regulation of transcription factors or RNA polymerase II, and maintaining the telomeres.
The U4 small nuclear Ribo-Nucleic Acid is a non-coding RNA component of the major or U2-dependent spliceosome – a eukaryotic molecular machine involved in the splicing of pre-messenger RNA (pre-mRNA). It forms a duplex with U6, and with each splicing round, it is displaced from the U6 snRNA in an ATP-dependent manner, allowing U6 to re-fold and create the active site for splicing catalysis. A recycling process involving protein Brr2 releases U4 from U6, while protein Prp24 re-anneals U4 and U6. The crystal structure of a 5′ stem-loop of U4 in complex with a binding protein has been solved.
snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein that in humans is encoded by the SNRNP70 gene. snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease. U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.
Pre-mRNA-processing-splicing factor 8 is a protein that in humans is encoded by the PRPF8 gene.
Splicing factor U2AF 35 kDa subunit is a protein that in humans is encoded by the U2AF1 gene.
Splicing factor 3 subunit 1 is a protein that in humans is encoded by the SF3A1 gene.
Heterogeneous nuclear ribonucleoprotein F is a protein that in humans is encoded by the HNRNPF gene.
Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene.
Splicing factor 3A subunit 2 is a protein that in humans is encoded by the SF3A2 gene.
Splicing factor 3B subunit 2 is a protein that in humans is encoded by the SF3B2 gene.
Splicing factor 3B subunit 4 is a protein that in humans is encoded by the SF3B4 gene.
Splicing factor 3B subunit 3 is a protein that in humans is encoded by the SF3B3 gene.
Pre-mRNA-processing factor 6 is a protein that in humans is encoded by the PRPF6 gene.
WD repeat domain 57 , also known as WDR57, is a gene found in many organisms, including, but not limited to Homo sapiens, Gallus gallus, Pan troglodytes, Canus familiaris, Bos taurus, Mus musculus, and Rattus norvegicus.
U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 2 is a protein that in humans is encoded by the ZRSR2 gene.
Prp24 is a protein part of the pre-messenger RNA splicing process and aids the binding of U6 snRNA to U4 snRNA during the formation of spliceosomes. Found in eukaryotes from yeast to E. coli, fungi, and humans, Prp24 was initially discovered to be an important element of RNA splicing in 1989. Mutations in Prp24 were later discovered in 1991 to suppress mutations in U4 that resulted in cold-sensitive strains of yeast, indicating its involvement in the reformation of the U4/U6 duplex after the catalytic steps of splicing.
RNA recognition motif, RNP-1 is a putative RNA-binding domain of about 90 amino acids that are known to bind single-stranded RNAs. It was found in many eukaryotic proteins.
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