Taspase1 processing alters TFIIA cofactor properties in the regulation of TFIID

Abstract

These authors contributed equally to this work.Keywords: core promoter, NC2, RNA polymerase II transcription, TFIID, TFIIA, Taspase1, TFIID regulation, TFIID promoter bindingAbbreviations: CPE, core promoter element; INR, initiator core promoter element; NC2, negative cofactor 2; RNAP II, RNA polymerase II; TBP, TATA-binding protein; TFII (TFIIA, -D), general transcription factor for RNA polymerase II.TFIIA is an important positive regulator of TFIID, the primary promoter recognition factor of the basal RNA polymerase II transcription machinery. TFIIA antagonises negative TFIID regulators such as negative cofactor 2 (NC2), promotes specific binding of the TBP subunit of TFIID to TATA core promoter sequence elements and stimulates the interaction of TBP-associated factors (TAFs) in the TFIID complex with core promoter elements located downstream of TATA, such as the initiator element (INR). Metazoan TFIIA consists of 3 subunits, TFIIAa (35 kDa), b (19 kDa) and g (12 kDa). TFIIAa and b subunits are encoded by a single gene and result from site-specific cleavage of a 55 kDa TFIIA (a/b) precursor protein by the protease Taspase1. Metazoan cells have been shown to contain variable amounts of TFIIA (55/12 kDa) and Taspase1-processed TFIIA (35/19/12 kDa) depending on cell type, suggesting distinct genespecific roles of unprocessed and Taspase1-processed TFIIA. How precisely Taspase1 processing affects TFIIA functions is not understood. Here we report that Taspase1 processing alters TFIIA interactions with TFIID and the conformation of TFIID/TFIIA promoter complexes. We further show that Taspase1 processing induces increased sensitivity of TFIID/TFIIA complexes to the repressor NC2, which is counteracted by the presence of an INR core promoter element. Our results provide first evidence that Taspase1 processing affects TFIIA regulation of TFIID and suggest that Taspase1 processing of TFIIA is required to establish INR-selective core promoter activity in the presence of NC2.

TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression

“…Oyama et al . did not analyse the effect of TFIIAα cleavage on Tbp recruitment and more recently it has been shown that TFIIAα cleavage affects Tbp/TFIID regulation 50 . As both Trf2 and Tbp were present at the promoters of haploid cell genes, the non-cleavage of TFIIAα could therefore affect transcription by via the activity of Trf2 and/or Tbp.…”

Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates through cleaving TFIIA

“…Complexes of TFIIAα-β/γ containing noncleaved TFIIAα-β have transcriptional activity in vitro, and its maturation into TFIIAα/β/γ increases its susceptibility to regulatory degradation ( 5 ). In addition, TFIIAα-β/γ and TFIIAα/β/γ are different in the pattern of interactions with TFIID, an important factor for promoter recognition ( 20 ). Since TBP-like protein was reported to be a negative regulator of the Taspase1-mediated processing of TFIIA, Taspase1 may fine-tune the transcription of genes through these factors ( 21 ).…”

Disease-relevant signalling-pathways in head and neck cancer: Taspase1’s proteolytic activity fine-tunes TFIIA function

“…In our present study containing only HPV-negative HNSCC tumours, we found a moderate but highly significant downregulation of p16 INK4a suggesting rather expressional downregulation than complete loss or silencing of the CDKN2A gene. It has been reported that Taspase1-mediated cleavage of TFIIA affects the conformation of TFIID/TFIIA promoter complexes and thus, enables assembly with TFIID and other tissue-specific transcription factors 53 . Thereby, Taspase1-mediated cleavage of TFIIA regulates tissue-specific expression profiles, e.g.…”