Biology subjects

M'Angale, P. G.

Publications and source records attributed to M'Angale, P. G..

3 recordsLinked to original sources

bioRxiv2026

Arc Capsids Facilitate the Transfer of Muscleblind.

The Drosophila activity-regulated cytoskeletal-associated protein (dArc1) can facilitate viral-like synaptic transfer of its own mRNA through dArc1 capsid formation. This transfer promotes synaptic maturation at the Drosophila neuromuscular junction and shows conservation to the mammalian neural synapse through the dArc1 mammalian ortholog, Arc. Recently, we established that dArc1 can interact with several transcripts other than its own in Drosophila including the transcript of muscleblind (Mbl), an RNA splicing factor known to be involved in neuronal and muscle development. Here, we demonstrate this interaction is further conserved to Arc and the mammalian Mbl ortholog Muscleblind Like Splicing Regulator 1 (Mbnl1). In the mouse neuro2a (N2A) cell line, immunoprecipitation of Arc protein enriches for both the Arc and Mbnl1 transcript. Upon differentiation of N2A cells, the ability of Arc to bind its own transcript and Mbnl1 are abolished while potassium stimulation of these cells restored Arc interactions with both transcripts, indicating that this interaction is enhanced by neuronal activity. This interaction is further conserved to the mammalian central nervous system, where Mbnl1 shows increased colocalization with Arc protein in the dentate gyrus of foot-shocked mice. Furthermore, we demonstrate that both Arc and Mbnl1 RNA can be detected in extracellular vesicles (EVs), and that Mbnl1, unlike the Arc transcript, is not directly encapsulated by Arc protein. We additionally observe MblA crosses the Drosophila NMJ, likely within EVs, and postsynaptic MblA accumulation is dependent on presynaptic pools of dArc1. Taken together, our data suggest that Arc protein interacts with Mbnl1 RNA in an activity-dependent manner and this interaction may facilitate transsynaptic transfer of Mbnl1 RNA through EVs with implications for neurodevelopment. SignificanceThe immediate early gene Arc is known to play roles in LTP, LTD, memory and is dysregulated in diseases of the CNS in addition to forming a viral-like capsid to allow for intercellular transfer of its own mRNA in a pathway referred to as the Viral-Like Synaptic Transfer of RNA (ViSyToR). Investigating additional members of the ViSyToR pathway will help increase our understanding of how Arc can play such diverse roles in the CNS. In this study, we establish that transcript for Muscleblind is an additional ViSyToR member in both Drosophila and the mammalian CNS.

neuroscience↗

bioRxiv2025

Imp, a key regulator of transposable elements, cell growth, and differentiation genes during embryogenesis

Imps are a highly conserved family of RNA-binding proteins involved in embryonic development, cancer progression, and neurogenesis. However, the molecular pathways and RNAs regulated by Imp to control these processes remain poorly understood. Embryos derived from Imp mutant germline clones arrest development, and transcriptome analysis revealed significant dysregulation of genes involved in cell growth, differentiation, tube morphogenesis, neuronal projection development, and RNA metabolism, along with de-repression of transposable element (TE) RNAs. Consistent with these findings, Imp mutant embryos display TE-overexpression phenotypes, are smaller in size, and exhibit defective organ development, including impaired tracheal branching and gastrulation. Reduced levels of Imp at the larval neuromuscular junction (NMJ) impair synaptic bouton formation and decrease adult longevity. RIP-seq experiments showed that Imp-associated RNAs are enriched for TE RNAs. Proteomic analyses confirmed that several TE-encoded proteins are upregulated in Imp mutant embryos. Specifically, the Ty1 family retrotransposon Copia was derepressed. Consistent with recent findings that Copia is a potent inhibitor of synaptogenesis, its upregulation likely contributes to the impaired NMJ formation and broader embryonic defects observed in Imp mutants. Moreover, Imp associates with piRNA pathway proteins, ensures Piwi nuclear localization, and--like piwi mutants--its loss disrupts TE silencing and causes position-effect variegation (PEV) defects. The analysis of Imp complexes further points to potential mechanisms by which Imp may regulate TE expression. Overall, these results indicate that Imp maintains genome stability and ensures proper developmental progression and neuronal activity by regulating post-transcriptional processes and suppressing transposons.

developmental biology↗

bioRxiv2023

Dueling Endogenous Viral-Like Sequences Control Synaptic Plasticity

The function of a large part of most genomes, generally called "junk DNA", remains largely unknown. Much of this enigmatic DNA corresponds to transposons, which are considered genomic parasites. Here, we show the protein of the Ty1 retrotransposon Copia is enriched at the Drosophila neuromuscular junction and is transported across synapses. Unexpectedly, disrupting Copia expression results in increases in both synapse development and structural synaptic plasticity. Plasticity is kept in balance as Copia antagonizes the Drosophila Arc (activity-regulated cytoskeleton-associated protein) homolog, which is a transposon-derived gene. Our cryo-EM structure of the Copia capsid shows a shell with large cargo capacity and leads to a hypothesis for mutual antagonism of Arc and Copia capsid assembly. Our findings provide evidence that a fully functional transposon plays a role at synapses, suggesting that transposons and other types of junk DNA are essential to developmental and cellular processes.

neuroscience↗