Academic Journal
The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer
| العنوان: | The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer |
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| المؤلفون: | Kouichi Kitamura, Tyuji Hoshino, Atsushi Okabe, Masaki Fukuyo, Bahityar Rahmutulla, Nobuko Tanaka, Sohei Kobayashi, Tomoaki Tanaka, Takashi Shida, Mashiro Ueda, Toshinari Minamoto, Hisahiro Matsubara, Atsushi Kaneda, Hideshi Ishii, Kazuyuki Matsushita |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 24, p 17341 (2023) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | FUBP1-interacting repressor (FIR), aberrant RNA splicing, ribosomal RNA (rRNA), RPB6 of RNA polymerase (RNAP), transcription factor IIH (TFIIH) P62 PH (pleckstrin homology), Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The interaction between mRNA and ribosomal RNA (rRNA) transcription in cancer remains unclear. RNAP I and II possess a common N-terminal tail (NTT), RNA polymerase subunit RPB6, which interacts with P62 of transcription factor (TF) IIH, and is a common target for the link between mRNA and rRNA transcription. The mRNAs and rRNAs affected by FUBP1-interacting repressor (FIR) were assessed via RNA sequencing and qRT-PCR analysis. An FIR, a c-myc transcriptional repressor, and its splicing form FIRΔexon2 were examined to interact with P62. Protein interaction was investigated via isothermal titration calorimetry measurements. FIR was found to contain a highly conserved region homologous to RPB6 that interacts with P62. FIRΔexon2 competed with FIR for P62 binding and coactivated transcription of mRNAs and rRNAs. Low-molecular-weight chemical compounds that bind to FIR and FIRΔexon2 were screened for cancer treatment. A low-molecular-weight chemical, BK697, which interacts with FIRΔexon2, inhibited tumor cell growth with rRNA suppression. In this study, a novel coactivation pathway for cancer-related mRNA and rRNA transcription through TFIIH/P62 by FIRΔexon2 was proposed. Direct evidence in X-ray crystallography is required in further studies to show the conformational difference between FIR and FIRΔexon2 that affects the P62–RBP6 interaction. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/24/17341; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067; https://doaj.org/article/a0cff5f04aac422ea084b85f427bed9b |
| DOI: | 10.3390/ijms242417341 |
| الاتاحة: | https://doi.org/10.3390/ijms242417341 https://doaj.org/article/a0cff5f04aac422ea084b85f427bed9b |
| رقم الانضمام: | edsbas.8FC6F046 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms242417341 |