The cytoplasmic SYNCRIP mRNA interactome of mammalian neurons

Khudayberdiev, Sharof; Soutschek, Michael; Ammann, Irina; Heinze, Anika; Rust, Marco B.; Baumeister, Stefan; Schratt, Gerhard

doi:10.1080/15476286.2020.1830553

Cited by 8 publications

(5 citation statements)

References 44 publications

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“…This isoform of Pros is not expressed earlier in development [ 180 ] but is necessary for production of larval neurons [ 179 ]. Similar mechanisms of mRNA regulation are observed in mammalian neurons where Syncrip regulates plasticity, neuronal development, and differentiation through 3′ UTR-mediated repression or stabilization of target mRNAs [ 181 ]. Thus, gene regulatory networks involving multiple RBPs and their respective targets can participate in temporal gene expression patterns that facilitate proper developmental transitions in neural stem cells.…”

Section: Regulation Of Temporal Gene Expressionmentioning

confidence: 81%

Emerging Roles of RNA-Binding Proteins in Neurodevelopment

Parra

Johnston

2022

JDB

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Diverse cell types in the central nervous system (CNS) are generated by a relatively small pool of neural stem cells during early development. Spatial and temporal regulation of stem cell behavior relies on precise coordination of gene expression. Well-studied mechanisms include hormone signaling, transcription factor activity, and chromatin remodeling processes. Much less is known about downstream RNA-dependent mechanisms including posttranscriptional regulation, nuclear export, alternative splicing, and transcript stability. These important functions are carried out by RNA-binding proteins (RBPs). Recent work has begun to explore how RBPs contribute to stem cell function and homeostasis, including their role in metabolism, transport, epigenetic regulation, and turnover of target transcripts. Additional layers of complexity are provided by the different target recognition mechanisms of each RBP as well as the posttranslational modifications of the RBPs themselves that alter function. Altogether, these functions allow RBPs to influence various aspects of RNA metabolism to regulate numerous cellular processes. Here we compile advances in RNA biology that have added to our still limited understanding of the role of RBPs in neurodevelopment.

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Section: Regulation Of Temporal Gene Expressionmentioning

confidence: 81%

Emerging Roles of RNA-Binding Proteins in Neurodevelopment

Parra

Johnston

2022

JDB

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“…Since Imp and Syp are highly conserved RBPs across the animal kingdom, we asked whether their RNA targets are also conserved. To this end, we compared our dataset with the RNA targets of human IMP1-3 in pluripotent stem cells (Conway et al, 2016) and murine Syncrip/hnRNPR in neural cells (Briese et al, 2018; Khudayberdiev et al, 2021). Within the genes that had high-confidence orthologues (DIOPT score > 8), we found a significant degree of conservation of RBP targets between fly and mammals: 76% (871/1144) for Imp and 55% (623/1134) for Syp (Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Human IMP1-3 eCLIP data from pluripotent stem cells were filtered for crosslink foldchange > 2 to identify IMP targets (Conway et al, 2016). Rat SYNCRIP iCLIP targets from primary neurons and mouse hnRNPR iCLIP targets from primary motoneurons and NSC34 (motoneuron-line) cell line were downloaded from following publications (Briese et al, 2018; Khudayberdiev et al, 2021). Human and murine genes were converted to fly genes using the DIOPT API tool, and only high-confidence orthologues (DIOPT score >= 8) were retained for comparisons.…”

Section: Methodsmentioning

confidence: 99%

“…exp_string: iCLIP RNA-binding protein and developmental stage; gene_id: FlyBase gene ID (Ensembl release 99); gene_name: FlyBase gene name; gene_biotype; gene biological type; n_binding_site: number of significant RBP binding sites; binding_feature: iCLIP binding site transcript features; l2fc_xlsite: log2FoldChange of crosslinks compared to SMInput across the entire gene body; padj_xlsite: adjusted p-value of crosslinks compared to SMInput across the entire gene body; l2fc_bsmax: log2Foldchange of the most enriched binding site compared to SMInput; padj_bsmin: minimum adjusted p-value within binding sites compared to SMInput; feature_pct: percentage of iCLIP binding sites overlapping with each transcript feature; avg_iCLIP_tpm: average crosslink transcripts per million; human_homologs: high confidence human homologs (DIOPT score > 7); mammalian_imp_target: conserved target with mammalian IMP1-3 in human pluripotent stem cells (Conway et al, 2016); mammalian_syp_target: conserved target with mammalian SYNCRIP or HNRNPR in rodent neurons (Briese et al, 2018; Khudayberdiev et al, 2021).…”

Section: Supplementary File Legendmentioning

confidence: 99%

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Imp and Sypin vivotemporal RNA interactomes uncover networks of temporal regulators ofDrosophilabrain development

Lee,

Huang,

Samuels

et al. 2024

Preprint

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Temporal patterning of neural progenitors is an evolutionarily conserved mechanism generating neural diversity. InDrosophila, post-embryonic neurogenesis requires the RNA-binding proteins (RBPs) Imp/IGF2BP and Syp/SYNCRIP. However, how they co-achieve their function is not well understood. Here, we elucidate thein vivotemporal RNA interactome landscapes of Imp and Syp during larval brain development. Imp and Syp bind a highly overlapping set of conserved mRNAs encoding proteins involved in neurodevelopment. We identify transcripts differentially occupied by Imp/Syp over time, featuring a network of known and novel candidate temporal regulators that are post-transcriptionally regulated by Imp/Syp. Furthermore, the physical and co-evolutionary relationships between Imp and Syp binding sites reveal a combinatorial, rather than competitive, mode of molecular interplay. Our study establishes a newin vivoframework for dissecting the temporal co-regulation of RBP networks as well as providing a resource for understanding neural fate specification.

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“…SYNCRIP and hnRNPU were identified among the top proteins associated with SERBP1 based on our proteomics analyses and gene expression correlations. SYNCRIP plays multiple roles in neuronal cells, including dendritic translation, synaptic plasticity, axonogenesis, and morphology (124)(125)(126)(127)(128). hnRNPU has been implicated in cortex development (129).…”

Section: Serbp1 Potential Role In Neurodegenerative Diseases and Neur...mentioning

confidence: 99%

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

Breunig,

Lei,

Montalbano

et al. 2024

Preprint

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RNA binding proteins (RBPs) containing intrinsically disordered regions (IDRs) are present in diverse molecular complexes where they function as dynamic regulators. Their characteristics promote liquid-liquid phase separation (LLPS) and the formation of membraneless organelles such as stress granules and nucleoli. IDR-RBPs are particularly relevant in the nervous system and their dysfunction is associated with neurodegenerative diseases and brain tumor development. SERBP1 is a unique member of this group, being mostly disordered and lacking canonical RNA-binding domains. Using a proteomics approach followed by functional analysis, we defined SERBP1’s interactome. We uncovered novel SERBP1 roles in splicing, cell division, and ribosomal biogenesis and showed its participation in pathological stress granules and Tau aggregates in Alzheimer’s disease brains. SERBP1 preferentially interacts with other G-quadruplex (G4) binders, implicated in different stages of gene expression, suggesting that G4 binding is a critical component of SERBP1 function in different settings. Similarly, we identified important associations between SERBP1 and PARP1/polyADP-ribosylation (PARylation). SERBP1 interacts with PARP1 and its associated factors and influences PARylation. Moreover, protein complexes in which SERBP1 participates contain mostly PARylated proteins and PAR binders. Based on these results, we propose a feedback regulatory model in which SERBP1 influences PARP1 function and PARylation, while PARylation modulates SERBP1 functions and participation in regulatory complexes.

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The cytoplasmic SYNCRIP mRNA interactome of mammalian neurons

Cited by 8 publications

References 44 publications

Emerging Roles of RNA-Binding Proteins in Neurodevelopment

Emerging Roles of RNA-Binding Proteins in Neurodevelopment

Imp and Sypin vivotemporal RNA interactomes uncover networks of temporal regulators ofDrosophilabrain development

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

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