HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8.
A genetic screen previously identified the N-terminal 91 amino acids of the eukaryotic initiation factor 3 subunit f (N91-eIF3f) as a potent inhibitor of HIV-1 replication. Overexpression of N91-eIF3f or full-length eIF3f reduced the level of HIV-1 mRNAs in the infected cell. Here we show that N91-eIF3f and eIF3f act by specifically blocking the 3' end processing of the HIV-1 pre-mRNA both in vivo and in vitro. Furthermore, the results suggest that eIF3f mediates this restriction of HIV-1 expression through the previously unsuspected involvement of a set of factors that includes eIF3f, the SR protein 9G8, and the cyclin-dependent kinase 11 (CDK11). eIF3f affects HIV-1 3' end processing by modulating the sequence-specific recognition of the HIV-1 pre-mRNA by 9G8.
Valente
Susana T
ST
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, HHSC 1310c, 701 West 168th Street, New York, NY 10032, USA. svalente@scripps.edu
Gilmartin
Greg M
GM
Venkatarama
Krishnan
K
Arriagada
Gloria
G
Goff
Stephen P
SP
D001483:Base Sequence; D001665:Binding Sites; D002457:Cell Extracts; D002467:Cell Nucleus / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism; D011485:Protein Binding; D026721:RNA 3' End Processing / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D014779:Virus Replication
D002457:Cell Extracts; D039621:Eukaryotic Initiation Factor-3; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D011061:Poly A; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases