Chrysovergis, K. | bioRxiv Science

bioRxiv2026

Short-term methionine starvation induces de novo diurnal oscillations of hepatic m6A RNA methylation

Dietary methionine restriction has been shown to improve metabolic health and treat multiple diseases. Methionine metabolism regulates transmethylation reactions, including N6-methyladenosine (m6A) RNA methylation, by modulating the availability of S-adenosyl methionine (SAM). Both m6A RNA methylation and methionine metabolism are involved in the regulation of the circadian clock. However, it remains unclear whether dietary methionine influences circadian rhythms through the regulation of m6A RNA modification. In this study, we investigated the effects of short-term methionine deprivation on the diurnal oscillations of m6A RNA methylation in the mouse liver. We found that a methionine-deficient (MD) diet reprogrammed the cyclic expression patterns of m6A writers, erasers, and readers. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that the MD diet induced de novo diurnal m6A oscillations in genes associated with RNA processing, protein translation, protein ubiquitination, and mTORC1 signaling pathways. RNA-seq and quantitative proteomics analyses demonstrated that MD-induced changes in m6A RNA levels were linked to alterations in mRNA and protein abundance. We observed that dynamic m6A RNA methylation of the transcripts encoding two key enzymes, MAT2A and CBS, helps maintain methionine homeostasis in response to methionine starvation. These findings identify m6A RNA methylation as a key mechanism linking methionine metabolism to circadian regulation.

molecular biology↗

bioRxiv2017

A class of GATA3 mutation reprograms the breast cancertranscriptional network through gain and loss of function

GATA3 is frequently mutated in breast cancer; these mutations are widely presumed to be loss of function. Here, we address molecular alterations downstream of a novel class of GATA3 mutations, revealing both gain and loss of function. Mutation of one allele of GATA3 led to loss of binding and decreased expression at a subset of genes, including Progesterone Receptor. At other loci, associated with epithelial to mesenchymal transition, gain of binding at a novel sequence motif correlated with increased gene expression. These results demonstrate that not all GATA3 mutations are equivalent and that these mutations impact breast cancer through gain and loss of function.

cell biology↗