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Splicing factor U2AF 65 kDa subunit is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''U2AF2''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.


Function

In
eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s, the
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
s in the transcribed
pre-mRNA A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by Transcription (genetics), transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcript ...
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 Small means of insignificant size Size in general is the Magnitude (mathematics), magnitude or dimensions of a thing. More specifically, ''geometrical size'' (or ''spatial size'') can refer to three geometrical measures: length, area, or ...
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
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
s early during spliceosome assembly. Multiple
alternatively spliced Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date. 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 RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcription (biology), transcript is transformed into a mature messenger RNA (Messenger RNA, mRNA). It works by removing all the introns (non-cod ...
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. The splicing factor U2AF65 can specifically recognize the
polypyrimidine tract {{Short description, A pyrimidine-rich sequence involved in pre-messenger RNA maturation The polypyrimidine tract is a region of pre-messenger RNA (mRNA) that promotes the assembly of the spliceosome, the protein complex specialized for carrying ...
(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. 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.


Interactions

U2AF2 has been shown to interact with: * PUF60, * SF1, * SFRS11, * SFRS2IP, * SRPK2, * U2 small nuclear RNA auxiliary factor 1 and *
WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...
.


References


Further reading

* * * * * * * * * * * * * * * * * * * {{PDB Gallery, geneid=11338