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Updated: Dec 16, 2025

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

Published on: December 5, 2016

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FMRP Regulates the Nuclear Export of Adam9 and Psen1 mRNAs: Secondary Analysis of an N6-Methyladenosine Dataset

Cara J Westmark1, Bryan Maloney2, Reid S Alisch3

  • 1Department of Neurology, University of Wisconsin-Madison, Madison, WI, USA. westmark@wisc.edu.

Scientific Reports
|July 3, 2020
PubMed

Insights

Fragile X mental retardation protein (FMRP) does not affect App mRNA nuclear export. However, N6-methyladenosine (m6A) modification patterns in FMRP targets, including APP processing enzymes, are altered in Fmr1 knockout mice.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Fragile X mental retardation protein (FMRP) regulates amyloid-beta precursor protein (App) mRNA translation, but the mechanism is unclear.
  • N6-methyladenosine (m6A) modification may influence App mRNA processing and FMRP binding.
  • APP processing is implicated in neurodegenerative disease phenotypes.

Purpose of the Study:

  • To investigate the roles of FMRP and m6A in the nuclear export of App mRNA.
  • To determine if FMRP deficiency impacts the cytoplasmic/nuclear abundance of App mRNA and related processing enzyme mRNAs.
  • To analyze m6A modification patterns in FMRP target mRNAs.

Main Methods:

  • Utilized m6A dataset to identify m6A sites in App mRNA.
  • Compared nuclear/cytoplasmic mRNA abundance in wild-type and Fmr1 knockout mouse brain cortex.
  • Validated FMRP targets and analyzed their m6A peaks and subcellular localization.

Main Results:

  • Fmr1 knockout did not alter the nuclear-cytoplasmic ratio of App mRNA.
  • Most validated FMRP targets (35/36) contained m6A peaks.
  • Agap2 mRNA was enriched in the nucleus of Fmr1 knockout mice, while Adam9 and Psen1 mRNAs were enriched in the cytoplasm of wild-type mice.

Conclusions:

  • FMRP and m6A do not appear to regulate App mRNA nuclear export.
  • FMRP deficiency alters m6A modification patterns in target mRNAs.
  • Specific APP processing enzyme mRNAs show altered subcellular localization in FMRP-deficient or wild-type states.

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