Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Ythdf is a N6-methyladenosine reader that modulates Fmr1 target mRNA selection and restricts axonal growth in Drosophila

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB
[thumbnail of Supporting Information] Other (Supporting Information)
6MB

Item Type:Article
Title:Ythdf is a N6-methyladenosine reader that modulates Fmr1 target mRNA selection and restricts axonal growth in Drosophila
Creators Name:Worpenberg, L., Paolantoni, C., Longhi, S., Mulorz, M.M., Lence, T., Wessels, H.H., Dassi, E., Aiello, G., Sutandy, F.X.R., Scheibe, M., Edupuganti, R.R., Busch, A., Möckel, M.M., Vermeulen, M., Butter, F., König, J., Notarangelo, M., Ohler, U., Dieterich, C., Quattrone, A., Soldano, A. and Roignant, J.Y.
Abstract:N6-methyladenosine (m(6)A) regulates a variety of physiological processes through modulation of RNA metabolism. This modification is particularly enriched in the nervous system of several species, and its dysregulation has been associated with neurodevelopmental defects and neural dysfunctions. In Drosophila, loss of m(6)A alters fly behavior, albeit the underlying molecular mechanism and the role of m(6)A during nervous system development have remained elusive. Here we find that impairment of the m(6)A pathway leads to axonal overgrowth and misguidance at larval neuromuscular junctions as well as in the adult mushroom bodies. We identify Ythdf as the main m(6)A reader in the nervous system, being required to limit axonal growth. Mechanistically, we show that the m(6)A reader Ythdf directly interacts with Fmr1, the fly homolog of Fragile X mental retardation RNA binding protein (FMRP), to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m(6)A pathway controls development of the nervous system and modulates Fmr1 target transcript selection.
Keywords:Fmr1, m(6)A, Nervous System, RNA Modification, Ythdf, Animals, Drosophila melanogaster
Source:EMBO Journal
ISSN:0261-4189
Publisher:EMBO Press / Wiley
Volume:40
Number:4
Page Range:e104975
Date:15 February 2021
Official Publication:https://doi.org/10.15252/embj.2020104975
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library