Biology subjects

Thomson, T.

Publications and source records attributed to Thomson, T..

9 recordsLinked to original sources

bioRxiv2026

The lncRNA Statera regulates synaptogenesis by repressing the retrotransposon copia in Drosophila

Retrotransposons are mobile genetic elements that can impair genome integrity, and their insertions and dysregulation have been implicated in various diseases. However, growing evidence suggests that retrotransposons may play important physiological roles. At the Drosophila larval neuromuscular junction (NMJ), the ViSyToR (Viral Synaptic Transfer of RNA) pathway requires the active retrotransposon copia as a key negative regulator of synaptogenesis. Here, we identify a long non-coding RNA, Statera (Stae), as a regulator of copia, initially discovered through its physical association with the Copia protein. Stae is highly expressed in the central nervous system and body wall muscles of Drosophila larvae. CRISPR knockout or RNAi knockdown of Stae leads to a general decrease of bouton number at the NMJ, indicating its role in promoting synaptogenesis. Furthermore, copia is highly upregulated in Stae mutants, suggesting that Stae functions to repress copia. Mechanistically, Stae reduces copia RNA stability and limits copia DNA copy number. Additional knockdown of copia in motor neuron-specific Stae RNAi animals rescues the abnormal NMJ morphology. Together, our findings reveal an unexpected role for a long non-coding RNA in promoting synaptogenesis by repressing a retrotransposon.

neuroscience↗

bioRxiv2026

Macroalgal fucoidan can activate the biological carbon pump

Macroalgae secrete complex carbohydrate polymers, their extracellular matrix, as protection against microbial degradation. By resisting breakdown, these carbohydrates can contribute to marine carbon sequestration, though mechanisms, extent, and timescales remain unknown. Using ship-based sampling and experiments, we found that brown macroalgae release 1.7-4.2% of carbon fixation as fucoidan, equivalent to 0.32-0.88 mg fucoidan per gram of dry seaweed tissue per day. A Bayesian model trained on our empirical data, coupled with Monte Carlo simulations suggests an annual global release of 13-37 megatons fucoidan carbon. Moreover, degradation resistance combined with surface-activity enabled fucoidan to act as glue that cross-linked allochthonous organic carbon including microbes and proteins into marine snow. Notably, substantial fucoidan exudation was universally conserved across all tested species and regions. Thus, any brown macroalgal species can be used e.g. via aquafarming to enhance the formation of marine snow.

ecology↗

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↗

bioRxiv2025

Somatic function of the Argonaute protein Aubergine is essential for neuromuscular development and function in Drosophila

BackgroundThe PIWI-interacting RNA (piRNA) pathway is the primary defense against the deleterious activity of transposable elements (TEs), a role classically assigned to the germline. We recently discovered that the retrotransposon Copia is a negative regulator of synaptogenesis at the Drosophila larval neuromuscular junction (LNMJ) [1]. Here, we investigated whether the piRNA pathway regulates Copia in this somatic context. MethodsAnalysis of existing sequencing data revealed the expression of piRNA pathway components in somatic tissues [2]. We focused on Aubergine (aub), a core PIWI-clade Argonaute. We utilized CRISPR generated aub reporter lines and confocal microscopy to confirm the enrichment of AUB at the LNMJ and next generation sequencing coupled with digital PCR to validate the upregulation of TEs in aub knockdown larvae and adult tissues. ResultsData from genetic reporters and antibody staining show that AUB is expressed and localized to the LNMJ. Tissue-specific knockdown of aub at the LNMJ resulted in increased TE expression, including Copia. In contrast to the synaptic overgrowth seen with Copia depletion [1], aub reduction caused a decrease in synapse number and impaired motor function and lifespan. These phenotypes are consistent with the upregulation of Copia, a negative regulator of synapse growth. ConclusionsOur findings demonstrate that AUB functions somatically at the LNMJ to repress TEs, thereby ensuring proper neuromuscular development and function. This work establishes a physiological role for the piRNA pathway in a somatic tissue, linking TE repression to neuromuscular development.

neuroscience↗

bioRxiv2025

Rlim coordinates diurnal regulation of food intake and thermogenesis

Energy homeostasis in mice is maintained through coordinated activity among hypothalamic nuclei that regulate food intake and thermogenesis. These processes must adapt to the sleep-wake cycle, yet the underlying pathways, cell types, and molecular mechanisms governing their diurnal regulation remain poorly understood. We show that mice lacking the E3 ubiquitin ligase Rlim are lean and resistant to diet-induced obesity, owing to reduced food intake and enhanced brown adipose tissue (BAT) thermogenesis. We identify GABAergic neurons in the suprachiasmatic nucleus (SCN)--components of the central circadian clock--as mediators of these effects. Specifically, Rlim in RIP-Cre+ neurons governs daily thermogenic rhythms, while Rlim in vasoactive intestinal peptide (VIP)-expressing neurons modulates diurnal feeding behavior. Thus, Rlim is a key regulator of diurnal rhythms controlling energy balance.

physiology↗

bioRxiv2024

An orbitocortical-thalamic circuit suppresses binge alcohol-drinking.

Alcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.

neuroscience↗

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↗

bioRxiv2021

Somatic piRNAs and Transposons are Differentially Regulated During Skeletal Muscle Atrophy and Programmed Cell Death

PiWi-interacting RNAs (piRNAs) are small single-stranded RNAs that can repress transposon expression via epigenetic silencing and transcript degradation. They have been identified predominantly in the ovary and testis, where they serve essential roles in transposon silencing in order to protect the integrity of the genome in the germline. The potential expression of piRNAs in somatic cells has been controversial. In the present study we demonstrate the expression of piRNAs derived from both genic and transposon RNAs in the intersegmental muscles (ISMs) from the tobacco hawkmoth Manduca sexta. These piRNAs are abundantly expressed, are ~27 nt long, map antisense to transposons, are oxidation resistant, exhibit a uridine bias at their first nucleotide, and amplify via the canonical ping-pong pathway. An RNA-seq analysis demonstrated that 20 piRNA pathway genes are expressed in the ISMs and are developmentally regulated. The abundance of piRNAs does not change when the muscles initiate developmentally-regulated atrophy, but are repressed when cells become committed to undergo programmed cell death at the end of metamorphosis. This change in piRNA expression is associated with the targeted repression of several retrotransposons and the induction of specific DNA transposons. The developmental changes in the expression of piRNAs, piRNA pathway genes, and transposons are all regulated by 20-hydroxyecdysone, the steroid hormone that controls the timing of ISM death. Taken together, these data provide compelling evidence for the existence of piRNA in somatic tissues and suggest that they may play roles in developmental processes such as programmed cell death. Author SummarypiRNAs are a class of small non-coding RNAs that suppress the expression of transposable elements, parasitic DNA that if reintegrated, can harm the integrity of the host genome. The expression of piRNAs and their associated regulatory proteins has been studied predominantly in germ cells and some stem cells. We have found that they are also expressed in skeletal muscles in the moth Manduca sexta that undergo developmentally-regulated atrophy and programmed cell death at the end of metamorphosis. The expression of transposons becomes deregulated when the muscles become committed to die, which may play a functional role in the demise of the cell by inducing genome damage. piRNA-mediated control of transposons may represent a novel mechanism that contributes to the regulated death of highly differentiated somatic cells.

developmental biology↗