Work

The RNA-binding protein FMRP facilitates the nuclear export of N6-methyladenosine–containing mRNAs

Year: 2019

Type: article

Abstract: N 6 -Methyladenosine (m 6 A) is the most abundant post-transcriptional mRNA modification in eukaryotes and exerts many of its effects on gene expression through reader proteins that bind specifically to m 6 A-containing transcripts. Fragile X mental retardation protein (FMRP), an RNA-binding protein, has previously been shown to affect the translation of target mRNAs and trafficking of mRNA granules. Loss of function of FMRP causes fragile X syndrome, the most common form of inherited intellectual disability in humans. Using HEK293T cells, siRNA-mediated gene knockdown, cytoplasmic and nuclear fractions, RNA-Seq, and LC-MS/MS analyses, we demonstrate here that FMRP binds directly to a collection of m 6 A sites on mRNAs. FMRP depletion increased mRNA m 6 A levels in the nucleus. Moreover, the abundance of FMRP targets in the cytoplasm relative to the nucleus was decreased in Fmr1 -KO mice, an effect also observed in highly methylated genes. We conclude that FMRP may affect the nuclear export of m 6 A-modified RNA targets.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.ac119.010078