Publication Date:
2016-10-14
Description:
Dietary calorie restriction is a broadly acting intervention that extends the lifespan of various organisms from yeast to mammals. On another front, magnesium (Mg 2+ ) is an essential biological metal critical to fundamental cellular processes and is commonly used as both a dietary supplement and treatment for some clinical conditions. If connections exist between calorie restriction and Mg 2+ is unknown. Here, we show that Mg 2+ , acting alone or in response to dietary calorie restriction, allows eukaryotic cells to combat genome-destabilizing and lifespan-shortening accumulations of RNA–DNA hybrids, or R-loops. In an R-loop accumulation model of Pbp1-deficient Saccharomyces cerevisiae , magnesium ions guided by cell membrane Mg 2+ transporters Alr1/2 act via Mg 2+ -sensitive R-loop suppressors Rnh1/201 and Pif1 to restore R-loop suppression, ribosomal DNA stability and cellular lifespan. Similarly, human cells deficient in ATXN2, the human ortholog of Pbp1, exhibit nuclear R-loop accumulations repressible by Mg 2+ in a process that is dependent on the TRPM7 Mg 2+ transporter and the RNaseH1 R-loop suppressor. Thus, we identify Mg 2+ as a biochemical signal of beneficial calorie restriction, reveal an R-loop suppressing function for human ATXN2 and propose that practical magnesium supplementation regimens can be used to combat R-loop accumulation linked to the dysfunction of disease-linked human genes.
Print ISSN:
0305-1048
Electronic ISSN:
1362-4962
Topics:
Biology
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