| Summary: | Summary: Recent studies have revealed a key role of PARP1 that catalyzes the poly-ADP-ribosylation (PARylation) of substrates in regulating gene transcription. We show here that HIV-1 transcriptional activation also requires PARP1 activity. Because efficient HIV-1 transactivation is known to depend on the ELL2-containing super elongation complex (SEC), we investigated the functional relationship between PARP1 and ELL2-SEC in HIV-1 transcriptional control. We show that PARP1 elevates ELL2 protein levels to form more ELL2-SEC in cells. This effect is caused by PARP1’s suppression of expression of Siah1, an E3 ubiquitin ligase for ELL2, at both mRNA and protein levels. At the mRNA level, PARP1 coordinates with the co-repressor NCoR to suppress Siah1 transcription. At the protein level, PARP1 promotes Siah1 proteolysis, likely through inducing PARylation-dependent ubiquitination (PARdU) of Siah1. Thus, a PARP1-Siah1 axis activates HIV-1 transcription and controls the expression of ELL2 and other Siah1 substrates. : Yu et al. reveal a critical role for a PARP1-Siah1 axis in controlling HIV-1 viral transcription. The axis increases cellular levels of the transcription factor ELL2 and its associated SEC complex that is required for robust HIV-1 transcription. Keywords: PARP1, Poly(ADP-Ribosyl)ation, PARylation, PARylation-dependent ubiquitination, PARdU, E3 ubiquitin ligase Siah1, HIV-1 transcription, ELL2, super elongation complex, SEC
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