Examination of the Unconventional Role of the 19S Proteasome Subcomplex in RNA Polymerase II Transcription in Saccharomyces cerevisiae

Conventionally, damaged and ubiquitinated proteins are subjected to degradation in the 26S proteasome in eukaryotes. However, several observations have indicated that the 19S subcomplex of the 26S proteasome may play a non-proteolytic role in RNA polymerase II (Pol II) transcription 1 : (1) Ubiquitination was thought to be required for activity of a viral transcription activator, VP16. (2) The transcription activation domains of several transcription activators including Myc overlap with the signal for ubiquitination. (3) Mutant alleles of yeast SUG1 and SUG2, two essential ATPases of the 19S proteasome subcomplex, could suppress the deficiencies of transcription activator and transcription elongation factor mutants. (4) Sug1p and Sug2p were found to directly bind to the activation domains of transcription activators such as Gal4p. (5) The 19S subcomplex coprecipitated with a yeast transcription elongation factor. (6) An anti-Sug1p antibody was reported to block transcription in vitro and addition of the purified 19S subcomplex restored the lost transcription activity. (7) A recent report 2 identified a novel complex, APIS (AAA proteins independent of 20S), originated from the 19S subcomplex. The APIS complex, which contains six ATPases including Sug1p and Sug2p, was recruited to actively transcribed genes through Gal4p in Saccharomyces cerevisiae. Together, these intriguing genetic and biochemical discoveries strongly suggest that the APIS complex of the 19S proteasome subcomplex is involved in RNA Pol II transcription in yeast. Although present observations suggest that the APIS complex plays a role in RNA Pol II transcription, it remains to be shown: (1) whether the recruitment of the APIS complex to the promoter by Gal4p is a pre-requisite for transcriptional activation of GAL genes and (2) in which steps of transcription complex assembly the APIS complex is involved.