Helmholtz Gemeinschaft


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

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supporting Information)

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. and Paolantoni, C. and Longhi, S. and Mulorz, M.M. and Lence, T. and Wessels, H.H. and Dassi, E. and Aiello, G. and Sutandy, F.X.R. and Scheibe, M. and Edupuganti, R.R. and Busch, A. and Möckel, M.M. and Vermeulen, M. and Butter, F. and König, J. and Notarangelo, M. and Ohler, U. and Dieterich, C. and Quattrone, A. and 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
Publisher:EMBO Press / Wiley
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 per month over past year

Open Access
MDC Library