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Maf1 limits RNA polymerase III-directed transcription to preserve genomic integrity and extend lifespan
Journal article   Open access   Peer reviewed

Maf1 limits RNA polymerase III-directed transcription to preserve genomic integrity and extend lifespan

Chiaki Noguchi, Lucy Wang, Mihir Shetty, Joshua Chang Mell, Christian Sell and Eishi Noguchi
Cell cycle (Georgetown, Tex.), v 20(3), pp 247-255
01 Feb 2021
PMID: 33475456
url
https://doi.org/10.1080/15384101.2021.1874697View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

aging genomic integrity Maf1 mTOR replication fork RNA polymerase III
A key to longevity assurance is the nutrient-sensing mTOR pathway. Inhibition of mTOR extends lifespan in a variety of organisms. However, the downstream effectors of the mTOR pathway for lifespan regulation are elusive. In a recent report, we described the role of Maf1 as a critical lifespan regulator downstream of the mTOR pathway in fission yeast. Maf1 is the master negative regulator of RNA polymerase III-directed transcription (e.g. tRNAs and 5S rRNAs) and is regulated by mTOR-mediated phosphorylation. We demonstrated that Maf1 is required for lifespan extension under calorie restriction or when mTOR is inhibited. We also showed that Maf1 prevents DNA damage at tRNA genes, which appears to contribute to lifespan maintenance by Maf1. Here we highlight these observations and present additional results to discuss the role of the mTOR-Maf1-Pol III axis in promoting genomic integrity in the face of DNA replication-transcription conflicts in order to maintain normal lifespan.

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Cell Biology
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