Editing Alternative splicing (section)

====Repressor-activator competition: HIV-1 ''tat'' exon 2====

[[File:Tat exon2 splicing.jpg|thumb|left|Alternative splicing of HIV-1 tat exon 2]]
[[HIV]], the [[retrovirus]] that causes [[AIDS]] in humans, produces a single primary RNA transcript, which is alternatively spliced in multiple ways to produce over 40 different mRNAs.<ref name=Zahler2004>{{cite journal | vauthors = Zahler AM, Damgaard CK, Kjems J, Caputi M | title = SC35 and heterogeneous nuclear ribonucleoprotein A/B proteins bind to a juxtaposed exonic splicing enhancer/exonic splicing silencer element to regulate HIV-1 tat exon 2 splicing | journal = The Journal of Biological Chemistry | volume = 279 | issue = 11 | pages = 10077–84 | date = March 2004 | pmid = 14703516 | doi = 10.1074/jbc.M312743200 | doi-access = free }}</ref> Equilibrium among differentially spliced transcripts provides multiple mRNAs encoding different products that are required for viral multiplication.<ref name=Jaquenet2001>{{cite journal | vauthors = Jacquenet S, Méreau A, Bilodeau PS, Damier L, Stoltzfus CM, Branlant C | title = A second exon splicing silencer within human immunodeficiency virus type 1 tat exon 2 represses splicing of Tat mRNA and binds protein hnRNP H | journal = The Journal of Biological Chemistry | volume = 276 | issue = 44 | pages = 40464–75 | date = November 2001 | pmid = 11526107 | doi = 10.1074/jbc.M104070200 | doi-access = free }}</ref> One of the differentially spliced transcripts contains the ''tat'' gene, in which exon 2 is a cassette exon that may be skipped or included. The inclusion of tat exon 2 in the RNA is regulated by competition between the splicing repressor hnRNP A1 and the SR protein SC35. Within exon 2 an exonic splicing silencer sequence (ESS) and an exonic splicing enhancer sequence (ESE) overlap. If A1 repressor protein binds to the ESS, it initiates [[cooperative binding]] of multiple A1 molecules, extending into the 5' donor site upstream of exon 2 and preventing the binding of the core splicing factor U2AF35 to the polypyrimidine tract. If SC35 binds to the ESE, it prevents A1 binding and maintains the 5' donor site in an accessible state for assembly of the spliceosome. Competition between the activator and repressor ensures that both mRNA types (with and without exon 2) are produced.<ref name=Zahler2004/>