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Abstract

Biological function relies on the precise control of gene expression. Genetic information is stored and transferred in the nucleic acids DNA and RNA, which are each composed of four canonical bases. While the sequence of bases in DNA and RNA are essential, they are not sufficient to convey genetic information at the level of intricacy needed to support biological function. Epigenetic modifications modify the flow of genetic information without changing nucleic acid sequence. Like epigenetic modifications on DNA and protein, post-transcriptional chemical modifications on RNA play important functional roles, governing RNA function and metabolism to control gene expression. N6-methyladenosine (m6A), the most abundant post-transcriptional mRNA modification in eukaryotes, exerts many of its effects on gene regulation through reader proteins that bind specifically to m6A-containing transcripts. This work characterizes the m6A binding specificities and biological functions of two proteins: YTH domain containing 2 (YTHDC2) and fragile X mental retardation protein (FMRP). We report that YTHDC2 and FMRP are readers of m6A that affect translation efficiency and nuclear export, respectively, and are essential for mammalian spermatogenesis and neural development.

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