A cell-type-specific alternative splicing regulator shapes synapse properties in a trans-synaptic manner

Schulz, Jan M.; Ortiz, Raul; Feng, Huijuan; Furlanis, Elisabetta; Gomez, Andrea M.; Schreiner, Dietmar; Bischofberger, Josef; Zhang, Chaolin; Scheiffele, Peter

doi:10.1016/j.celrep.2023.112173

Cited by 12 publications

(10 citation statements)

References 89 publications

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“…For immunohistochemistry, brain sections were processed as previously described (Traunmuller et al ., 2023). In brief, brain slices were kept for 1.5 h with a PBS-based blocking solution containing 0.1% Triton X-100 and 5% normal donkey serum (NDS) and subsequently incubated with primary antibodies in blocking solution at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

“…The CLIP experiments were performed according to the seCLIP protocol (Van Nostrand et al ., 2017b) with some minor modifications (Traunmuller et al ., 2023). Olfactory bulbs from seven mice were pooled for each biological replicate and for heart tissue one heart was used per biological replicate.…”

Section: Methodsmentioning

confidence: 99%

“…Such cell type-specific isoform repertoires arise from the combinatorial action of multiple, broadly expressed RBPs, but can also be instructed by alternative splicing factors with selective expression in specific neuronal populations (Iijima et al, 2014;Norris et al, 2014;Traunmüller et al, 2014;Jacko et al, 2018;Saito et al, 2019;Traunmuller et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, deep mapping of neuronal transcript isoforms uncovered that even closely related cell types express highly divergent alternative splice isoforms of synaptic proteins and ion channels (Wamsley et al , 2018; Furlanis et al , 2019; Saito et al , 2019; Feng et al , 2021; Ha et al , 2021). Such cell type-specific isoform repertoires arise from the combinatorial action of multiple, broadly expressed RBPs, but can also be instructed by alternative splicing factors with selective expression in specific neuronal populations (Iijima et al , 2014; Norris et al , 2014; Traunmüller et al , 2014; Jacko et al , 2018; Saito et al ., 2019; Traunmuller et al , 2023).…”

Section: Introductionmentioning

confidence: 99%

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Dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons

Di Bartolomei,

Ortiz,

Schreiner

et al. 2023

Preprint

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Precise coordination of molecular programs and neuronal growth govern the formation, maintenance, and adaptation of neuronal circuits. RNA metabolism has emerged as a key regulatory node of neural development and nervous system pathologies. To uncover novel cell-type-specific RNA regulators, we systematically investigated expression of RNA recognition motif-containing proteins in the mouse neocortex. Surprisingly, we found RBM20, an alternative splicing regulator associated with dilated cardiomyopathy, to be expressed in cortical parvalbumin interneurons and mitral cells of the olfactory bulb. Genome-wide mapping of RBM20 target mRNAs revealed that neuronal RBM20 binds distal intronic regions. Loss of neuronal RBM20 has only modest impact on alternative splice isoforms but results in a significant reduction in an array of mature mRNAs in the neuronal cytoplasm. This phenotype is particularly pronounced for genes with long introns that encode synaptic proteins. We hypothesize that RBM20 ensures fidelity of pre-mRNA splicing by suppressing non-productive splicing events in long neuronal genes. This work highlights a common requirement of two excitable cell types, cardiomyocytes and neurons, for RBM20-dependent transcriptome regulation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons

Di Bartolomei,

Ortiz,

Schreiner

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Multiple isoforms can be produced via either alternative RNA splicing or promoter usage. To date, substantial research has focused on the regulation of alternative splicing of synapse organizers (e.g., neurexin isoforms) 78 , leaving the transcriptional mechanisms underlying alternative promoter usage poorly understood. Our work uncovered a transcriptional mechanism for the spatial (neuron type-specific) regulation of two different isoforms (produced via alternative promoter usage) of the same synapse organizer (MADD-4/Punctin) in C. elegans neuromuscular synapses.…”

Section: Neuron Type-specific Regulation Of Synapse Organizersmentioning

confidence: 99%

UNC-30/PITX coordinates neurotransmitter identity with postsynaptic GABA receptor clustering

Correa,

Mialon,

Cizeron

et al. 2024

Preprint

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Terminal selectors are transcription factors that control neuronal identity by regulating the expression of key effector molecules, such as neurotransmitter (NT) biosynthesis proteins, ion channels and neuropeptides. Whether and how terminal selectors control neuronal connectivity is poorly understood. Here, we report that UNC-30 (PITX2/3), the terminal selector of GABA motor neuron identity in C. elegans, is required for NT receptor clustering, a hallmark of postsynaptic differentiation. Animals lacking unc-30 or madd-4B, the short isoform of the MN-secreted synapse organizer madd-4 (Punctin/ADAMTSL), display severe GABA receptor type A (GABAAR) clustering defects in postsynaptic muscle cells. Mechanistically, UNC-30 acts directly to induce and maintain transcription of madd-4B and GABA biosynthesis genes (e.g., unc-25/GAD, unc-47/VGAT). Hence, UNC-30 controls GABAAR clustering on postsynaptic muscle cells and GABA biosynthesis in presynaptic cells, transcriptionally coordinating two critical processes for GABA neurotransmission. Further, we uncover multiple target genes and a dual role for UNC-30 both as an activator and repressor of gene transcription. Our findings on UNC-30 function may contribute to our molecular understanding of human conditions, such as Axenfeld-Rieger syndrome, caused by PITX2 and PITX3 gene mutations.

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Transition to Piscivory Seen Through Brain Transcriptomics in a Juvenile Percid Fish: Complex Interplay of Differential Gene Transcription, Alternative Splicing, and ncRNA Activity

Symonová,

Jůza,

Tesfaye

et al. 2024

J Exp Zool Pt A

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Pikeperch (Sander Lucioperca) belongs to main predatory fish species in freshwater bodies throughout Europe playing the key role by reducing planktivorous fish abundance. Two size classes of the young‐of‐the‐year (YOY) pikeperch are known in Europe and North America. Our long‐term fish survey elucidates late‐summer size distribution of YOY pikeperch in the Lipno Reservoir (Czechia) and recognizes two distinct subcohorts: smaller pelagic planktivores heavily outnumber larger demersal piscivores. To explore molecular mechanisms accompanying the switch from planktivory to piscivory, we compared brain transcriptomes of both subcohorts and identified 148 differentially transcribed genes. The pathway enrichment analyses identified the piscivorous phase to be associated with genes involved in collagen and extracellular matrix generation with numerous Gene Ontology (GO), while the planktivorous phase was associated with genes for non‐muscle‐myosins (NMM) with less GO terms. Transcripts further upregulated in planktivores from the periphery of the NMM network were Pmchl, Pomcl, and Pyyb, all involved also in appetite control and producing (an)orexigenic neuropeptides. Noncoding RNAs were upregulated in transcriptomes of planktivores including three transcripts of snoRNA U85. Thirty genes mostly functionally unrelated to those differentially transcribed were alternatively spliced between the subcohorts. Our results indicate planktivores as potentially driven by voracity to initiate the switch to piscivory, while piscivores undergo a dynamic brain development. We propose a spatiotemporal spreading of juvenile development over a longer period and larger spatial scales through developmental plasticity as an adaptation to exploiting all types of resources and decreasing the intraspecific competition.

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A cell-type-specific alternative splicing regulator shapes synapse properties in a trans-synaptic manner

Cited by 12 publications

References 89 publications

Dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons

Dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons

UNC-30/PITX coordinates neurotransmitter identity with postsynaptic GABA receptor clustering

Transition to Piscivory Seen Through Brain Transcriptomics in a Juvenile Percid Fish: Complex Interplay of Differential Gene Transcription, Alternative Splicing, and ncRNA Activity

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