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Mol Cell. 2009 Oct 23;36(2):279-89. doi: 10.1016/j.molcel.2009.10.004.

HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8.

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Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, HHSC 1310c, 701 West 168th Street, New York, NY 10032, USA.


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.

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