FMRP Regulates the Nuclear Export of Adam9 and Psen1 mRNAs: Secondary Analysis of an N6-Methyladenosine Dataset
Abstract Fragile X mental retardation protein (FMRP) binds to and regulates the translation of amyloid-β protein precursor ( App ) mRNA, but the detailed mechanism remains to be determined. Differential methylation of App mRNA could underlie FMRP binding, message localization and translation efficie...
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Published in | Scientific reports Vol. 10; no. 1; p. 10781 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group
01.07.2020
Nature Publishing Group UK |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
Fragile X mental retardation protein (FMRP) binds to and regulates the translation of amyloid-β protein precursor (
App
) mRNA, but the detailed mechanism remains to be determined. Differential methylation of
App
mRNA could underlie FMRP binding, message localization and translation efficiency. We sought to determine the role of FMRP and N
6
-methyladeonsine (m
6
A) on nuclear export of
App
mRNA. We utilized the m
6
A dataset by Hsu and colleagues to identify m
6
A sites in
App
mRNA and to determine if the abundance of message in the cytoplasm relative to the nucleus is altered in
Fmr1
knockout mouse brain cortex. Given that processing of APP to Aβ and soluble APP alpha (sAPPα) contributes to disease phenotypes, we also investigated whether
Fmr1
KO
associates with nuclear export of the mRNAs for APP protein processing enzymes, including β-site amyloid cleaving enzyme (Bace1), A disintegrin and metalloproteinases (Adams), and presenilins (Psen).
Fmr1
KO
did not alter the nuclear/cytoplasmic abundance of
App
mRNA. Of 36 validated FMRP targets, 35 messages contained m
6
A peaks but only
Agap2
mRNA was selectively enriched in
Fmr1
KO
nucleus. The abundance of the APP processing enzymes
Adam9
and
Psen1
mRNA, which code for a minor alpha-secretase and gamma-secretase, respectively, were selectively enriched in wild type cytoplasm. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-020-66394-y |