Human immunodeficiency virus type 1 hnRNP A/B-dependent exonic splicing silencer ESSV antagonizes binding of U2AF65 to viral polypyrimidine tracts.
Human immunodeficiency virus type 1 (HIV-1) exonic splicing silencers (ESSs) inhibit production of certain spliced viral RNAs by repressing alternative splicing of the viral precursor RNA. Several HIV-1 ESSs interfere with spliceosome assembly by binding cellular hnRNP A/B proteins. Here, we have further characterized the mechanism of splicing repression using a representative HIV-1 hnRNP A/B-dependent ESS, ESSV, which regulates splicing at the vpr 3' splice site. We show that hnRNP A/B proteins bound to ESSV are necessary to inhibit E complex assembly by competing with the binding of U2AF65 to the polypyrimidine tracts of repressed 3' splice sites. We further show evidence suggesting that U1 snRNP binds the 5' splice site despite an almost complete block of splicing by ESSV. Possible splicing-independent functions of U1 snRNP-5' splice site interactions during virus replication are discussed.
Domsic
Jeffrey K
JK
Program in Molecular Biology, University of Iowa, Iowa City, Iowa 52242, USA.
Wang
Yibin
Y
Mayeda
Akila
A
Krainer
Adrian R
AR
Stoltzfus
C Martin
CM
D001483:Base Sequence; D005091:Exons; D020868:Gene Silencing; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009687:Nuclear Proteins; D011485:Protein Binding; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism; D000072668:Splicing Factor U2AF
D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009687:Nuclear Proteins; D012342:RNA, Small Nuclear; D012367:RNA, Viral; D012191:Retroviridae Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C405483:U1 small nuclear RNA; C000607494:U2AF2 protein, human