Nucleolar TFIIE plays a role in ribosomal biogenesis and performance
| Autor: | Tamara Phan, Pallab Maity, Christina Ludwig, Lisa Streit, Miltiadis Tsesmelis, Sebastian Iben, Karin Scharffetter-Kochanek, Jens Michaelis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Proteasome Endopeptidase Complex
Hot Temperature Transcription Genetic AcademicSubjects/SCI00010 Ribosome biogenesis RNA polymerase II Biology Ribosome Transcription Factors TFII Transcription (biology) Genes Reporter RNA Polymerase I Genetics RNA polymerase I Humans Trichothiodystrophy Syndromes Luciferases Molecular Biology Cell Line Transformed Organelle Biogenesis General transcription factor Protein Stability RNA Ribosomal RNA Fibroblasts Cell biology Gene Expression Regulation RNA Ribosomal Protein Biosynthesis Mutation biology.protein Proteostasis Ribosomes Transcription Factor TFIIH Cell Nucleolus |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Ribosome biogenesis is a highly energy-demanding process in eukaryotes which requires the concerted action of all three RNA polymerases. In RNA polymerase II transcription, the general transcription factor TFIIH is recruited by TFIIE to the initiation site of protein-coding genes. Distinct mutations in TFIIH and TFIIE give rise to the degenerative disorder trichothiodystrophy (TTD). Here, we uncovered an unexpected role of TFIIE in ribosomal RNA synthesis by RNA polymerase I. With high resolution microscopy we detected TFIIE in the nucleolus where TFIIE binds to actively transcribed rDNA. Mutations in TFIIE affects gene-occupancy of RNA polymerase I, rRNA maturation, ribosomal assembly and performance. In consequence, the elevated translational error rate with imbalanced protein synthesis and turnover results in an increase in heat-sensitive proteins. Collectively, mutations in TFIIE—due to impaired ribosomal biogenesis and translational accuracy—lead to a loss of protein homeostasis (proteostasis) which can partly explain the clinical phenotype in TTD. |
| Databáze: | OpenAIRE |
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