Understanding regulation of HIV-1 gene expression by Sam68ΔC. (A) Following transcription, HIV-1 RNA undergoes alternative splicing to generate over 40 mRNAs that correspond to unspliced (encoding Gag and Gagpol), singly spliced (to produce Vif, Vpr, Vpu and Env) or multiply spliced (for generating Tat, Rev and Nef) mRNAs. Unspliced and singly spliced viral RNAs are exported to the cytoplasm via exportin-1, which is mediated by Rev, while the multiply spliced RNAs exit using Nxf1. Once within the cytoplasm, Sam68ΔC interacts with the unspliced, singly spliced and nef mRNAs to block their translation by preventing the binding of PABP1 (shown as a small blue circle). In contrast, PABP1 binds to tat and rev mRNAs, and translation is unaffected. (B) A model for the discrimination between tat, rev and nef mRNAs. The process of splicing used to generate the mRNAs encoding Tat, Rev and Nef results in slight variations in 5' sequence, but all the mRNAs encompass the nef reading frame (individual reading frames are illustrated by block arrows). However, translation of the individual reading frames could result in variations in the composition/structure of the mRNA within the common sequence (as represented by the coloured ovals). Such differences in composition/structure of the viral mRNP could serve as means by which Sam68ΔC selectively regulates their expression.