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N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO
FTO exhibits efficient oxidative demethylation activity of abundant N6-methyladenosine (m6A) residues in RNA in vitro, and it is shown that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO. Expand
A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation
It is reported here that human METTL14 catalyzes m6A RNA methylation, and together with METTL3, the only previously known m 6A methyltransferase, these two proteins form a stable heterodimer core complex ofMETTL3-14 that functions in cellular m6 a deposition on mammalian nuclear RNAs. Expand
Global Epigenomic Reconfiguration During Mammalian Brain Development
The results extend the knowledge of the unique role of DNA methylation in brain development and function, and offer a new framework for testing the role of the epigenome in healthy function and in pathological disruptions of neural circuits. Expand
ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.
The discovery of ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo strongly suggests that the reversible m( 6)A modification has fundamental and broad functions in mammalian cells. Expand
N 6 -methyladenosine Modulates Messenger RNA Translation Efficiency
In a unified mechanism of m(6)A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereasYTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m( 6)A. Expand
YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA
All three YTHDF proteins may act in an integrated and cooperative manner to impact fundamental biological processes related to m6A RNA methylation in the cytoplasm. Expand
Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome
Application of Tet-assisted bisulfite sequencing to embryonic stem cells not only confirms widespread distribution of 5hmC in the mammalian genome but also reveals sequence bias and strand asymmetry at5hmC sites. Expand
Programming and Inheritance of Parental DNA Methylomes in Mammals
It is found that 5mC or its oxidized derivatives, at the majority of demethylated CpGs, are converted to unmodified cytosines independent of passive dilution from gametes to four-cell embryos. Expand
m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.
This work uncovers a critical function for ALKBH5 and provides insight into critical roles of m6A methylation in glioblastoma and a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of AL KBH5 withFOXM1 nascent transcripts. Expand
Dynamic RNA Modifications in Gene Expression Regulation
Roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes are revealed. Expand