RT Journal Article
SR Electronic
T1 The m<sup>6</sup>A reader Ythdf restricts axonal growth in <em>Drosophila</em> through target selection modulation of the Fragile X mental retardation protein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.04.976886
DO 10.1101/2020.03.04.976886
A1 Alessia Soldano
A1 Lina Worpenberg
A1 Chiara Paolantoni
A1 Sara Longhi
A1 Miriam M. Mulorz
A1 Tina Lence
A1 Hans-Hermann Wessels
A1 Giuseppe Aiello
A1 Michela Notarangelo
A1 FX Reymond Sutandy
A1 Marion Scheibe
A1 Raghu R. Edupuganti
A1 Anke Busch
A1 Martin M. Möckel
A1 Michiel Vermeulen
A1 Falk Butter
A1 Julian König
A1 Uwe Ohler
A1 Christoph Dieterich
A1 Alessandro Quattrone
A1 Jean-Yves Roignant
YR 2020
UL http://biorxiv.org/content/early/2020/03/05/2020.03.04.976886.abstract
AB N6-methyladenosine (m6A) regulates a variety of physiological processes through modulation of RNA metabolism. The 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 m6A alters fly behavior albeit the underlying mechanism and the role of m6A during nervous system development have remained elusive. Here we find that impairment of the m6A 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 m6A reader in the nervous system being required for limiting axonal growth. Mechanistically, we show that Ythdf directly interacts with Fragile X mental retardation protein to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m6A pathway controls development of the nervous system by modulating Fmr1 target selection.