A Role of the C-terminal Part of p44 in the Promoter Escape Activity of Transcription Factor IIH

Tremeau‐Bravard, Alexandre; Pérez, C.; Egly, Jean‐Marc

doi:10.1074/jbc.m102457200

Cited by 26 publications

(25 citation statements)

References 34 publications

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“…9). These observations strongly suggest that p44 is involved in the transition stage, which confirms observations made previously (46,53). The bHLH and bHL regions of hTFIIE␤ may play distinct roles before and at transcription initiation.…”

Section: Discussionsupporting

confidence: 78%

“…These observations support the notion that, once transcription is initiated at the initiation site of supercoiled templates, no additional requirements are needed to complete transcription, probably because the torsional stress from negative supercoiling is converted into the energy needed to open up the dsDNA, thereby allowing Pol II transcription to proceed (9,39). In contrast, extension of initiated transcripts through the transcription transition stage (promoter escape) might require TFIIH helicase activity when linearized templates are used (3,6,17,53). Thus, our observations as well as the data presented by Tremeau-Bravard and colleagues showing p44 involvement in the transcription transition stage (promoter escape) (53) clearly indicate that transcription with a supercoiled template reflects transcription initiation activity while transcription with a linearized template reflects the ability to transit from transcription initiation to elongation.…”

supporting

confidence: 62%

“…Thus, it appears that p44 function may be affected by the mutations in the bHL C-terminal helix and loop. This is quite intriguing because p44 has recently been reported to play a role in promoter escape, which occurs at the transition stage (53). Furthermore, p44 acts together with XPD to tightly associate with CAK (3,4,46).…”

Section: Vol 23 2003 Functional Residues In Human Tfiie␤ 2919mentioning

confidence: 99%

“…C-terminal bHL residues are involved in the transition from transcription initiation to elongation by binding to p44. It is believed that transcription with a supercoiled template reflects transcription initiation activity while transcription with a linearized template reflects the activity to transit from transcription initiation to elongation (6,9,39,53,56). In our previous paper, we studied the activity of TFIIE in three in vitro transcription assays, namely, an assay of transcription with a supercoiled template, an abortive initiation assay examining the addition of one nucleotide at the initiation site, and an assay of transcription with a linearized template (56).…”

mentioning

confidence: 99%

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The Carboxy Terminus of the Small Subunit of TFIIE Regulates the Transition from Transcription Initiation to Elongation by RNA Polymerase II

Watanabe

Hayashi

Tanaka

et al. 2003

Molecular and Cellular Biology

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The general transcription factor TFIIE plays essential roles in both transcription initiation and the transition from initiation to elongation. Previously, we systematically deleted the structural motifs and characteristic sequences of the small subunit of human TFIIE (hTFIIE␤) to map its functional regions. Here we introduced point mutations into two regions located near the carboxy terminus of hTFIIE␤ and identified the functionally essential amino acid residues that bind to RNA polymerase II (Pol II), the general transcription factors, and single-stranded DNA. Although most residues identified were essential for transcription initiation, use of an in vitro transcription assay with a linearized template revealed that several residues in the carboxyterminal helix-loop region are crucially involved in the transition stage. Mutations in these residues also affected the ability of hTFIIE␤ to stimulate TFIIH-mediated phosphorylation of the carboxy-terminal heptapeptide repeats of the largest subunit of Pol II. Furthermore, these mutations conspicuously augmented the binding of hTFIIE␤ to the p44 subunit of TFIIH. The antibody study indicated that they thus altered the conformation of one side of TFIIH, consisting of p44, XPD, and Cdk-activating kinase subunits, that is essential for the transition stage. This is an important clue for elucidating the molecular mechanisms involved in the transition stage.In eukaryotes, the expression of protein-coding genes is strictly regulated at the level of transcription by RNA polymerase II (Pol II). Once signals from outside the nucleus are received and the condensed form of the inactive chromatin is activated and remodeled by chromatin-modulating factors, five general transcription factors (TFIIB, TFIID, TFIIE, TFIIF, and TFIIH) together with Pol II form the preinitiation complex (PIC) on the core promoter. Formation of this complex is assisted by various transcriptional activators, cofactors, and mediators (for reviews, see references 19, 25, and 43). Analyses of the PIC assembly pathway using isolated general transcription factors have revealed that the factors can assemble stepwise in vitro. This process commences with the binding of TFIID to the TATA box on the core promoter and ends with TFIIE and TFIIH joining the PIC (reviewed in references 10, 26, 34, and 42). It is widely accepted that TFIIE and TFIIH stabilize and activate the PIC by binding to all the other general transcription factors as well as to Pol II and at the same time open up the double-stranded DNA (dsDNA) at the region from Ϫ9 to ϩ2, adjacent to the transcription initiation site (ϩ1), in a manner that is dependent on dATP hydrolysis (14,56). This process is known as promoter melting. These various functions of TFIIE and TFIIH have been revealed recently by three types of studies. First, photo-cross-linking studies demonstrated that TFIIE␤ binds directly to the core promoter region between positions Ϫ14 and Ϫ2, which is where the promoter melts upon transcription initiation (5, 41). Second, two-dimensiona...

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Section: Discussionsupporting

confidence: 78%

supporting

confidence: 62%

Section: Vol 23 2003 Functional Residues In Human Tfiie␤ 2919mentioning

confidence: 99%

mentioning

confidence: 99%

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The Carboxy Terminus of the Small Subunit of TFIIE Regulates the Transition from Transcription Initiation to Elongation by RNA Polymerase II

Watanabe

Hayashi

Tanaka

et al. 2003

Molecular and Cellular Biology

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“…Prediction algorithms of miRNA target sites (miRGator) confirmed that these seven TFIIH-coding mRNAs are potentially targeted by miRNAs (Table S1). Because the p44 subunit plays a role in RNA pol II promoter-escape modulating transcription (27) and its coding mRNA presents only three predicted miRNA binding sites (miR-27a, miR-27b, miR-189), we focused our study on p44 mRNA. To experimentally identify miRNAs regulating p44 mRNA translation/stability, we used a method that allows the identification of miRNAs binding to a particular 3′ UTR in vivo (28) and further validated the interaction by intracellular localization/interaction with the RISC complex.…”

Section: Tfiih-coding Mrnas Are Regulated At the Posttranscriptional mentioning

confidence: 99%

MicroRNA-27a regulates basal transcription by targeting the p44 subunit of general transcription factor IIH

Portal

2011

Proc. Natl. Acad. Sci. U.S.A.

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General transcription factor IIH (TFIIH) is a complex RNA polymerase II basal transcription factor comprising 10 different polypeptides that display activities involved in transcription and DNA repair processes. Although biochemical studies have uncovered TFIIH importance, little is known about how the mRNAs that code for TFIIH subunits are regulated. Here it is shown that mRNAs encoding seven of the TFIIH subunits (p34, p44, p52, p62, XPB, CDK7, and p8) are regulated at the posttranscriptional level in a Dicer-dependent manner. Indeed, abolition of the miRNA pathway induces abnormal accumulation, stabilization, and translational activation of these seven mRNAs. Herein, miR-27a was identified as a key regulator of p44 mRNA. Moreover, miR-27a was shown to destabilize the p44 subunit of the TFIIH complex during the G2-M phase, thereby modulating the transcriptional shutdown observed during this transition. This work is unique in providing a demonstration of global transcriptional regulation through the action of a single miRNA.T o maintain cellular homeostasis, cells have evolved a myriad of specialized pathways, among which basal transcription and DNA repair play crucial roles. Both mechanisms are mainly regulated by the multisubunit complex termed TFIIH (general transcription factor IIH) formed by two modules, the core and the CAK [cyclin-dependent kinase (CDK)-activated kinase], each displaying distinguishable activities and differential protein composition (1-3). Whereas the core is constituted by seven polypeptides (p34, p44, p52, p62, XPB, XPD, and p8) and is indispensable for transcription and DNA repair (4), the CAK contains only three proteins (CDK7, CycH, and MAT1) and is required to modulate transcription by phosphorylating the carboxyl terminal domain of RNA polymerase II (5). Moreover, the CAK module regulates cellcycle progression by phosphorylating CDKs during G2-M transition in an autonomous fashion (6).Mutations in different TFIIH subunits lead to severe clinical disorders that range from mental retardation to cancer predisposition. This predisposition is manifested in patients displaying three clinically well-characterized syndromes-Xeroderma Pigmentosum, Cockaine syndrome, and Trichothiodystrophyhighlighting the importance of maintaining TFIIH integrity (7-9). Lessons learned from mutations encountered on patients helped to unravel which activities of TFIIH were modified in different clinical contexts. However, it has not been possible either to link specific mutations with a particular syndrome or with clinical severity (10-12). Nevertheless, all three clinical anomalies are taught, in principle, to be caused by diminished transcriptional and DNA repair activities often associated with reduced TFIIH stability. In vitro-obtained data show that naturally occurring mutations in XPD or p44 that alter the XPD/p44 or p44/p62 interaction may affect the composition of TFIIH by decreasing levels of XPD and CAK subunits associated with the core. On the other hand, mutations in XPB and p52 may prevent XPB...

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Components of nucleotide excision repair and DNA damage tolerance in Arabidopsis thaliana

Kunz

Anderson

Osmond

et al. 2005

Environ and Mol Mutagen

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As obligate phototrophs, and despite shielding strategies, plants sustain DNA damage caused by UV radiation in sunlight. By inhibiting DNA replication and transcription, such damage may contribute to the detrimental effects of UV radiation on the growth, productivity, and genetic stability of higher plants. However, there is evidence that plants can reverse UV-induced DNA damage by photoreactivation or remove it via nucleotide excision repair. In addition, plants may have mechanisms for tolerating UV photoproducts as a means of avoiding replicative arrest. Recently, phenotypic characterization of plant mutants, functional complementation studies, and cDNA analysis have implicated genes isolated from the model plant Arabidopsis thaliana in nucleotide excision repair or tolerance of UV-induced DNA damage. Here, we briefly review features of these processes in human cells, collate information on Arabidopsis homologs of the relevant genes, and summarize the experimental findings that link certain of these plant genes to nucleotide excision repair or damage tolerance.

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A Role of the C-terminal Part of p44 in the Promoter Escape Activity of Transcription Factor IIH

Cited by 26 publications

References 34 publications

The Carboxy Terminus of the Small Subunit of TFIIE Regulates the Transition from Transcription Initiation to Elongation by RNA Polymerase II

The Carboxy Terminus of the Small Subunit of TFIIE Regulates the Transition from Transcription Initiation to Elongation by RNA Polymerase II

MicroRNA-27a regulates basal transcription by targeting the p44 subunit of general transcription factor IIH

Components of nucleotide excision repair and DNA damage tolerance in Arabidopsis thaliana

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