Recent studies aimed at elucidating the mechanism controlling HIV-1 transcription have led to the identification and characterization of two multi-subunit complexes that both contain
P-TEFb, a human transcription
elongation factor and co-factor for activation of HIV-1 gene expression by the viral
Tat protein. The first complex, termed the 7SK
snRNP, acts as a reservoir where active
P-TEFb can be withdrawn by Tat to stimulate HIV-1 transcription. The second complex, termed the super elongation complex (SEC), represents the form of
P-TEFb delivered by Tat to the paused
RNA polymerase II at the viral long terminal repeat during Tat transactivation. Besides
P-TEFb, SEC also contains other elongation factors/co-activators, and they cooperatively stimulate HIV-1 transcription. Recent data also indicate SEC as a target for the mixed lineage
leukemia (MLL)
protein to promote the expression of MLL target genes and leukemogenesis. Given their roles in HIV-1/
AIDS and
cancer, further characterization of 7SK
snRNP and SEC will help develop strategies to suppress aberrant transcriptional elongation caused by uncontrolled
P-TEFb activation. As both complexes are also important for normal cellular gene expression, studying their structures and functions will elucidate the mechanisms that control metazoan transcriptional elongation in general.