Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30192228.
- Also identified by DOI 10.7554/eLife.35447 and PMC identifier 6128692.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Transcription by RNA polymerase III (Pol III) is an essential cellular process, and mutations in Pol III can cause neurodegenerative disease in humans. However, in contrast to Pol II transcription, which has been extensively studied, the knowledge of how Pol III is regulated is very limited. We report here that in budding yeast, <i>Saccharomyces cerevisiae</i>, Pol III is negatively regulated by the <u>S</u>mall <u>U</u>biquitin-like <u>MO</u>difier (SUMO), an essential post-translational modification pathway. Besides sumoylation, Pol III is also targeted by ubiquitylation and the Cdc48/p97 segregase; these three processes likely act in a sequential manner and eventually lead to proteasomal degradation of Pol III subunits, thereby repressing Pol III transcription. This study not only uncovered a regulatory mechanism for Pol III, but also suggests that the SUMO and ubiquitin modification pathways and the Cdc48/p97 segregase can be potential therapeutic targets for Pol III-related human diseases.
Medical subject headings
- RNA Polymerase III
- Saccharomyces cerevisiae
- Signal Transduction
- Small Ubiquitin-Related Modifier Proteins
- Ubiquitin
- Valosin Containing Protein