Biology subjects

Laneve, P.

Publications and source records attributed to Laneve, P..

4 recordsLinked to original sources

bioRxiv2026

nHOTAIRM1 scaffolds ANXA11-dependent assemblies to drive axonal mRNA localization in human motor neurons

Long noncoding RNAs (lncRNAs) are well recognized as regulators of neuronal development and function, yet their integration into canonical axonal transport pathways, an essential component of spatial gene regulation in highly polarized cells, remains incompletely defined. It is still unclear to what extent individual lncRNAs confer cargo selectivity and couple discrete mRNA cohorts to established transport machineries. Here we identify a cytoplasmic role for the neuronal isoform of HOTAIRM1 (nHOTAIRM1) in shaping the axonal RNA landscape of human iPSC-derived spinal motor neurons (spMNs). We show that nHOTAIRM1 associates with Annexin A11 (ANXA11), a factor linked to lysosome-coupled movement of RNA granules and engages a defined subset of MN-relevant mRNAs. Transcriptome-wide and targeted interaction assays, together with computational mapping and steric competition, support direct RNA-RNA pairing between nHOTAIRM1 and mRNAs involved in cytoskeletal organization and synaptic or vesicular functions, while spatial analyses place these RNA pairs in close proximity within the soma and neurites. Loss-of-function experiments further show that nHOTAIRM1 depletion reduces the association of these mRNAs with ANXA11-positive complexes and diminishes their enrichment in neuronal projections, an effect that is recapitulated by ANXA11 depletion. Collectively, these findings support a model in which nHOTAIRM1 contributes to the selective recruitment of cargo mRNAs into ANXA11-associated transport assemblies, thereby promoting their localization within distal neurites. More broadly, our findings provide mechanistic insight into how a lncRNA can regulate mRNA sorting and compartment-specific RNA trafficking in human spMNs.

molecular biology↗

bioRxiv2024

A circuit involving the lncRNA MB3 and the driver genes MYC and OTX2 inhibits apoptosis in Group 3 Medulloblastoma by regulating the TGF-β pathway via HMGN5

BackgroundGroup 3 (G3) is one of the most common, aggressive and fatal subtypes of the paediatric cerebellar tumour Medulloblastoma (MB), primarily driven by the MYC oncogene. Targeting MYC has long been challenging and this, combined with our incomplete understanding of G3 MB molecular bases, has hindered the development of effective targeted therapies. Long noncoding RNAs (lncRNAs), with their extensive oncogenic roles, cancer-specific expression, and connection to MYC biology, offer opportunities for unravelling this complexity and providing new insights and therapeutic targets. MethodologyUsing genome-wide, molecular and cellular assays, we characterised the activity of the MYC-dependent, anti-apoptotic lncRNA lncMB3 in G3 MB cells. ResultsThrough transcriptomic and interactomic analyses, we clarified lncMB3 function and mode-of-action. LncMB3 controls the TGF-{beta} pathway, critically altered in G3 medulloblastomagenesis. This regulation occurs via the direct coding-noncoding RNA interaction between lncMB3 and the mRNA for the epigenetic factor HMGN5, with both sharing targets in the TGF-{beta} cascade. This axis converges on apoptosis through OTX2, another G3 MB driver gene, and photoreceptor lineage genes. Synergistic effects between lncMB3 targeting and cisplatin treatment underscores the relevance of this regulatory network in vitro. Finally, we propose novel ferritin-based nanocarriers as efficient delivery tools for antisense oligonucleotides targeting lncMB3. ConclusionsLncMB3 emerges as a central node linking MYC amplification to apoptosis inhibition through a circuit involving RNA-based mechanisms, G3 MB key drivers and underexplored factors. This integrated framework deepens our understanding of G3 MB molecular underpinnings and lay the foundation for translating lncRNA research into potential applications.

cancer biology↗

bioRxiv2024

Genome biology of long non-coding RNAs in humans: a virtual karyotype

BackgroundLong non-coding RNAs (lncRNAs) represent a unique and groundbreaking class of RNA molecules that exert regulatory functions with remarkable tissue and cellular specificities. Although the number of identified functional lncRNAs is increasing, comprehensive profiling of lncRNA genomics remains elusive. Creating a virtual lncRNA karyotype is especially important for species whose intrinsic features enable their biosynthesis and function in context-dependent manners. Results and conclusionsTo address this challenge, we employed existing annotation files to create a statistical genomics portrait of lncRNA genes for comparison with protein-coding genes. We provide a foundational reference for exploring the non-coding genome, offering insights into the genomic characteristics of lncRNAs that may enhance understanding of their biological significance and impact.

genomics↗

bioRxiv2024

Live-cell imaging of circular and long non-coding RNAs associated to FUS pathological aggregates by Pepper fluorescent RNA

Lately, important advancements in visualizing RNAs in fixed and live cells have been achieved. While mRNA imaging techniques are well-established, the development of effective methods for studying non-coding RNAs (ncRNAs) in living cells are still challenging but necessary, as they cover a variety of function and of intracellular localization, including highly dynamic processes like phase-transition, still poorly studied in vivo. Addressing this issue, we tagged two exemplary ncRNAs with the innovative fluorescent RNA (fRNA) Pepper. Specifically, we show circ-HDGFRP3 interaction with p-bodies, we recapitulate its recruitment in pathological FUS aggregates in a dynamic fashion and we super-resolve its distribution in such aggregates via Structured Illumination Microscopy. Moreover, we tracked the long non-coding RNA (lncRNA) nHOTAIRM1, a motor neurons-specific constituent of stress granules (SG), monitoring its behavior throughout the oxidative-stress response in physiological and pathological conditions. Overall, as fRNAs development advances, our work shows a successful use of Pepper for the monitoring of complex processes, as phase-transition, of paradigmatic molecules like circular RNAs (circRNAs) and lncRNAs with super-resolution potential in living mammalian cells.

molecular biology↗