Mechanistic study of non-proteolytic roles of the proteasome in suppressing cryptic transcription

Abstract

One of great advance in twenty years is that the 26S proteasome, known only as a molecular trashcan before, actually governs many cellular processes non-proteolytically. Cumulative evidence indicates that the proteasome is important for recruitment of activators and co-activators to promoters, ubiquitin-dependent histone modification, transcriptional elongation, maturation of mRNA via the facilitation of mRNA export from the nucleus to the cytoplasm and DNA repair. Here, I found unique evidences that the base sub-complex of the proteasome is involved in suppressing cryptic transcription initiation by interacting with yChd1p which has ATP-dependent chromatin remodeling activity and known to be important for H3K36 methylation. I found that non-proteolytic mutant of the proteasome, sug1-25, showed increased H3K4 methylation level in cryptic TATA site and was sensitive to pGal1-FLO8-His3 reporter assay. Moreover, double mutation of the 19S RP and CHD1 gene generates more short transcripts in FLO8 region. These data implicate that base complex of 26S proteasome is involved in cryptic transcription. Interestingly, biochemical activity of yChd1p is stimulated by the 19S RP in the presence of ATP. This study describes direct link between the non-proteolytic role of proteasome and cryptic transcription and provides specific mechanism governs the phenomenon above.

Keywords: 19S proteasome, Cryptic transcription, yChd1p, Nucleosome remodeling