Summary: New research from NYU Abu Dhabi explains how a tiny chemical modification on messenger RNA — known as m6A methylation — helps organize the developing brain. The study shows m6A controls the production of proteins required for axon growth, notably APC and β-actin, and that disrupting this mechanism can affect neural circuit formation and has been associated with neurodevelopmental disorders such as autism and schizophrenia.
Researchers found that this subtle molecular tag influences where and when specific proteins are made inside neurons, enabling precise local control of the cellular machinery that builds and extends axons. Because axons are the long processes neurons use to reach and communicate with their targets, accurate local protein production is vital for wiring neural circuits during development. The team’s findings emphasize how small biochemical changes inside cells can ripple outward to influence brain structure and function.
Key Facts:
- RNA methylation role: m6A methylation tunes local protein synthesis in neurons and helps direct axon growth.
- Critical proteins: APC (adenomatous polyposis coli) organizes neuronal architecture and supports the local production of β-actin, a core cytoskeletal component that drives axon extension.
- Clinical connections: Genetic mutations that affect m6A machinery have been linked to altered APC regulation and are associated with conditions such as autism and schizophrenia.
Source: NYU
Research team and context
A multidisciplinary group in the RNA-MIND Lab at NYU Abu Dhabi, led by Professor Dan Ohtan Wang and including research associate Belal Shohayeb, describes these findings in a paper published in Cell Reports. Their work focuses on m6A — a common methyl modification of adenosine residues in mRNA — and how this mark affects the translation of messages that code for proteins critical to neuronal morphology.
The study demonstrates that m6A modification helps regulate global production of APC protein in neuronal cell bodies through interactions with YTH domain-containing reader proteins. APC, in turn, is necessary for the transport and local translation of β-actin mRNA in axons and growth cones. Local synthesis of β-actin builds and remodels the cytoskeleton where and when it is needed, enabling axon extension and guidance.
Importantly, the team reports that disrupting components of the m6A pathway — either by reducing the activity of the m6A writer enzyme METTL14 or the reader protein YTHDF1, or by introducing human missense mutations in METTL14 linked to neurodevelopmental disorders — impairs APC expression. This disruption decreases the proper axonal localization and translation of β-actin, leading to defective axon development in both cellular experiments and animal models.
“This research links a global regulatory process — how proteins are synthesized across the cell — with highly localized effects that shape neuron structure and connectivity,” said Professor Ohtan Wang. “When these finely tuned molecular systems malfunction, the consequences can be reflected in neurodevelopmental conditions. Understanding these mechanisms gives us new insight into how brain wiring is established and how it may go awry.”
By clarifying how an m6A-dependent pathway controls the expression and local action of an RNA-binding protein (APC), the study provides a clear molecular route by which global gene-expression mechanisms influence the precise placement and timing of protein synthesis in axons. This improves our understanding of fundamental neurodevelopmental processes and highlights molecular nodes that could be relevant for future therapeutic or diagnostic approaches.
About this genetics, mental health, and neurodevelopment research news
Author: Adam Pockriss
Source: NYU
Contact: Adam Pockriss – NYU
Image: The image is credited to Neuroscience News
Original Research: Open access. “m6A RNA methylation-mediated control of global APC expression is required for local translation of β-actin and axon development” by Dan Ohtan Wang et al., published in Cell Reports (DOI: http://dx.doi.org/10.1016/j.celrep.2025.115727).
Abstract
m6A RNA methylation-mediated control of global APC expression is required for local translation of β-actin and axon development
Neuronal development relies on spatial control of mRNA localization and translation, mediated by RNA-binding proteins. This study identifies the adenomatous polyposis coli protein (APC) as encoded by mRNA modified with N6-methyladenosine (m6A). m6A modification promotes APC translation in neuronal cell bodies through YTH domain-containing reader proteins. Reduced expression of the m6A writer METTL14 or the reader YTHDF1, or expression of METTL14 variants carrying human missense mutations associated with autism and schizophrenia, leads to disrupted APC expression. Such disruption impairs the axonal transport and local translation of APC-regulated β-actin mRNA in axons and growth cones, which in turn hinders axon development both in vitro and in vivo. These results reveal a mechanism where m6A-regulated global expression of an RNA-binding protein governs local axonal mRNA translation and proper neural circuit formation.