Three human RNA polymerases interact with TFIIH via a common RPB6 subunit

Okuda, Masahiko; Suwa, Tetsufumi; Suzuki, Haruo; Yamaguchi, Yuki; Nishimura, Yoshifumi

doi:10.1093/nar/gkab612

Cited by 17 publications

(14 citation statements)

References 59 publications

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“…Figure 6b shows that DR-BERT predicts with high confidence that the N-terminal tail of RPB6 is in fact disordered. Indeed, NMR spectroscopy shows that not only does RPB6 have a flexible N-terminal tail, this tail is also used to bind to the p62 subunit of the TFIIH transcription factor( Okuda et al, 2021 ). Figure 6a shows DR-BERT’s predictions overlaid on the NMR-determined structure of the complex between RPB6 and the TFIIH p62 PH domain (PDB: 7DTI).…”

Section: Resultsmentioning

confidence: 99%

DR-BERT: A Protein Language Model to Annotate Disordered Regions

Nambiar

Forsyth

Liu

et al. 2023

Preprint

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Despite their lack of a rigid structure, intrinsically disordered regions in proteins play important roles in cellular functions, including mediating protein-protein interactions. Therefore, it is important to computationally annotate disordered regions of proteins with high accuracy. Most popular tools use evolutionary or biophysical features to make predictions of disordered regions. In this study, we present DR-BERT, a compact protein language model that is first pretrained on a large number of unannotated proteins before being trained to predict disordered regions. Although it does not use any evolutionary or biophysical information, DR-BERT shows a statistically significant improvement when compared to several existing methods on a gold standard dataset. We show that this performance is due to the information learned during pre-training and DR-BERT's ability to use contextual information. A web application for using DR-BERT is available at https://huggingface.co/spaces/nambiar4/DR-BERT and the code to run the model can be found at https://github.com/maslov-group/DR-BERT.

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Section: Resultsmentioning

confidence: 99%

DR-BERT: A Protein Language Model to Annotate Disordered Regions

Nambiar

Forsyth

Liu

et al. 2023

Preprint

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“…The Rpb4/Rpb7 heterodimer is neither essential for elongation nor included in the Pol II core [ 13 , 14 ]. Rpb6 is involved in contact with TFIIS and TFIIH [ 39 , 40 ], neither of which was present in the transcription complex on the (-) viroid RNA template. This is in line with our recent observation that TFIIS is dispensable for PSTVd replication [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

A remodeled RNA polymerase II complex catalyzing viroid RNA-templated transcription

Mudiyanselage

Pechan

et al. 2022

PLoS Pathog

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Viroids, a fascinating group of plant pathogens, are subviral agents composed of single-stranded circular noncoding RNAs. It is well-known that nuclear-replicating viroids exploit host DNA-dependent RNA polymerase II (Pol II) activity for transcription from circular RNA genome to minus-strand intermediates, a classic example illustrating the intrinsic RNA-dependent RNA polymerase activity of Pol II. The mechanism for Pol II to accept single-stranded RNAs as templates remains poorly understood. Here, we reconstituted a robust in vitro transcription system and demonstrated that Pol II also accepts minus-strand viroid RNA template to generate plus-strand RNAs. Further, we purified the Pol II complex on RNA templates for nano-liquid chromatography-tandem mass spectrometry analysis and identified a remodeled Pol II missing Rpb4, Rpb5, Rpb6, Rpb7, and Rpb9, contrasting to the canonical 12-subunit Pol II or the 10-subunit Pol II core on DNA templates. Interestingly, the absence of Rpb9, which is responsible for Pol II fidelity, explains the higher mutation rate of viroids in comparison to cellular transcripts. This remodeled Pol II is active for transcription with the aid of TFIIIA-7ZF and appears not to require other canonical general transcription factors (such as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, and TFIIS), suggesting a distinct mechanism/machinery for viroid RNA-templated transcription. Transcription elongation factors, such as FACT complex, PAF1 complex, and SPT6, were also absent in the reconstituted transcription complex. Further analyses of the critical zinc finger domains in TFIIIA-7ZF revealed the first three zinc finger domains pivotal for RNA template binding. Collectively, our data illustrated a distinct organization of Pol II complex on viroid RNA templates, providing new insights into viroid replication, the evolution of transcription machinery, as well as the mechanism of RNA-templated transcription.

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“…Moreover, transcription and translation are inhibited by heat stress‐induced oxidative DNA damage (Belhadj Slimen et al, 2014), making time for the repair mechanisms, to restore the damages. The repair mechanisms and transcription are tightly regulated and the intimate structural link between them appears to be TFIIH, a transcription initiation factor of all three different RNA polymerases, which contains ERCC3, GTF2H3 and GTF2H4 among others (Okuda et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Genetic diversity and thermotolerance in Holstein cows: Pathway analysis and marker development using whole‐genome sequencing

Kalemkeridou

Nanas

Moutou

et al. 2022

Reprod Domestic Animals

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Heat stress causes extensive losses in the dairy sector, due to negative effects on milk production and reproduction. Cows have evolved a series of protective mechanisms, (physiological, biochemical, behavioural) to cope with the thermostressing environments, which have allowed the preservation of productive and reproductive potential of specific animals during summer; these animals are considered thermotolerant and could be used to design programs of selective breeding. These programs, targeting the generations of a population of heat‐resistant animals, would increase the frequency of the desired phenotypes, tackling the financial losses on one hand and reducing the carbon footprints of the dairy sector on the other. The development of genomics techniques has enabled genome wide variant calling, to detect SNPs associated with the desired phenotypes. In this study, we used a comparative genomics approach to detect genetic variation associated with thermotolerance and to design molecular markers for characterizing the animals as tolerant/sensitive. A total of 40 cows from each group were split in four sequencing pools and a whole‐genome sequencing approach was used. Results and conclusion: Genome‐wide genetic variation between groups was characterized and enrichment analysis revealed specific pathways which participate in the adaptive mechanisms of thermotolerance, implicated into systemic and cellular responses, including the immune system functionality, Heat Stress and Unfolded Protein Response. The markers made a promising set of results, as specific SNPs in five genes encoding for Heat Shock Proteins were significantly associated with thermotolerance.

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Three human RNA polymerases interact with TFIIH via a common RPB6 subunit

Cited by 17 publications

References 59 publications

DR-BERT: A Protein Language Model to Annotate Disordered Regions

DR-BERT: A Protein Language Model to Annotate Disordered Regions

A remodeled RNA polymerase II complex catalyzing viroid RNA-templated transcription

Genetic diversity and thermotolerance in Holstein cows: Pathway analysis and marker development using whole‐genome sequencing

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