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Liver-specific Mettl14 deletion induces nuclear heterotypia and dysregulates RNA export machinery

ABSTRACT: Modification of RNAs with N6-methadenosine (m6A) has gained attention in recent years as a general mechanism of gene regulation. In the liver, m6A and its associated machinery has been studied as a potential biomarker of disease and cancer, with impacts on metabolism, cell cycle regulation, and pro-cancer state signaling. In vivo studies have begun to explore the effects of m6A in the liver, but differences in outcome of deletion of m6A writers Mettl3 and Mettl14 have not been thoroughly described or explained. Similarly, in vivo studies of the effects of m6A readers such as Ythdf1 and Ythdf2 have not been extended to characterize impacts of dysregulation of these reader proteins in the liver. To understand Mettl14 function, as well as Ythdf1 and Ythdf2, we developed mouse models and found a Mettl14 deletion specific phenotype of progressive liver injury characterized by nuclear heterotypia, with studies highlighting changes in mRNA splicing, processing and export leading to increases in mRNA surveillance and recycling.

ORGANISM(S): Mus musculus

PROVIDER: GSE265879 | GEO | 2024/06/18

REPOSITORIES: GEO

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N6-methyladenosine Modulates Messenger RNA Translation Efficiency

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