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The m6A(m)-independent role of FTO in regulating WNT signaling pathways

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Title
The m6A(m)-independent role of FTO in regulating WNT signaling pathways
Author(s)
Hyunjoon Kim; Soohyun Jang; Lee, Young-Suk
Publication Date
2022-05
Journal
Life science alliance, v.5, no.5
Publisher
NLM (Medline)
Abstract
© 2022 Kim et al.FTO and ALKBH5 are the two enzymes responsible for mRNA demethylation. Hence, the functional study of FTO has been focused on its mechanistic role in dynamic mRNA modification, and how this post-transcriptional regulation modulates signaling pathways. Here, we report that the functional landscape of FTO is largely associated with WNT signaling pathways but in a manner that is independent of its enzymatic activity. Re-analyses of public datasets identified the bifurcation of canonical and noncanonical WNT pathways as the major role of FTO. In FTO-depleted cells, we find that the canonical WNT/β-Catenin signaling is attenuated in a non-cell autonomous manner via the up-regulation of DKK1. Simultaneously, this up-regulation of DKK1 promotes cell migration via activating the noncanonical WNT/PCP pathway. Unexpectedly, this regulation of DKK1 is independent of its RNA methylation status but operates at the transcriptional level, revealing a noncanonical function of FTO in gene regulation. In conclusion, this study places the functional context of FTO at the branch point of multiple WNT signaling pathways and extends its mechanistic role in gene regulation.
URI
https://pr.ibs.re.kr/handle/8788114/11240
DOI
10.26508/lsa.202101250
ISSN
2575-1077
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
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