Regulation and outcomes of localized <scp>RNA</scp> translation

Gasparski, Alexander N.; Mason, Devon E.; Moissoglu, Konstadinos; Mili, Stavroula

doi:10.1002/wrna.1721

Cited by 32 publications

(21 citation statements)

References 150 publications

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“…While patterns emerge, such as an enrichment of CDS binding events in transcripts localized to the cell edge or 3’ UTR binding events and nuclear edge localization, the correlations are weak. This reflects the complexity of factors driving RNA localization and RBP-RNA spatiotemporal relationships, such as compartment-specific localization and function of RBPs and their interactors 60 .…”

Section: Resultsmentioning

confidence: 99%

Bento: A toolkit for subcellular analysis of spatial transcriptomics data

Mah

Ahmed

Lopez³

et al. 2022

Preprint

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Advances in spatial transcriptomics technologies produce RNA imaging data at increasingly higher throughput and scale. Current computational methods identify and measure the spatial relationships between cell-types, but do not leverage the spatial information of individual RNA molecules to reveal subcellular spatiotemporal dynamics of RNA processing. Here, we developed Bento, a computational framework for subcellular analysis of high-throughput spatial transcriptomics datasets. Bento handles single-molecule data generated by diverse spatial transcriptomics technologies and computes spatial statistics of subcellular RNA molecular distributions, compartmental expression, and cell morphology to build multidimensional feature sets for exploratory analysis. We also developed a multi-label ensemble model for generalizable classification of subcellular localization of every gene in every cell. To demonstrate Bento's utility, we applied it to analyze spatial transcriptomics datasets generated by seqFISH+ (10k genes in ~200 fibroblast cells) and MERFISH (130 genes quantified in ~1000 U2-OS cells) to understand the interplay between gene function, cellular morphology and RNA localization. To understand the role of RNA localization in RNA processing, we integrated spatial data with RNA binding protein (RBP) binding data to explore the spatiotemporal dynamics of RBP-RNA interactions at unprecedented scale (3,165 RNA species x 148 RBPs). We found RNA targets of individual RBPs to be enriched in specific subcellular compartments — such as Splicing Factor 3a Protein Complex (SF3A3), and that preferential localization is influenced by RBP binding of genomic regions for RBPs including Staufen homolog 2 (STAU2). Bento builds on the existing ecosystem of single-cell and spatial analysis toolkits, to ensure accessibility and community-driven tool development. We provide Bento as an open-source tool for the community to further expand our understanding of subcellular biology.

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Section: Resultsmentioning

confidence: 99%

Bento: A toolkit for subcellular analysis of spatial transcriptomics data

Mah

Ahmed

Lopez³

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Several splicing factors, including catenin β -like 1(CTNNBL1) and ubiquitin-specific peptidase 39 (USP39), could promote the growth and invasion of OV cells ( Li et al, 2017 ; Wang et al, 2021 ). The intranuclear genetic information could be transferred into the cytoplasm through RNA transport, participating in cancer pathogenesis and therapeutic response ( Gasparski et al, 2022 ). DNA replication is a key step in maintaining genome stability and is frequently disrupted in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The Roles of Drug Metabolism-Related ADH1B in Immune Regulation and Therapeutic Response of Ovarian Cancer

Peng

Kang

et al. 2022

Front. Cell Dev. Biol.

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Background: The different pharmacological effects of drugs in different people can be explained by the polymorphisms of drug metabolism-related genes. Emerging studies have realized the importance of drug metabolism-related genes in the treatment and prognosis of cancers, including ovarian cancer (OV). In this study, using comprehensive bioinformatics and western blot, we identified that the drug metabolism-related gene, ADH1B, was significantly down-regulated in OV cells and tissues. The patients with a high level of ADH1B presented a good prognosis. We also found a negative correlation between ADH1B expression and the activity of chemotherapeutic agents, such as cyclophosphamide. In addition, positive correlations were observed between ADH1B expression and multiple immune checkpoints, including LAG3 and HAVCR2. The immune infiltration analysis further indicated that aberrantly expressed ADH1B might have important roles in regulating the infiltration of macrophages and neutrophils in OV tissues. Then, the co-expression analysis was conducted and the top three enriched KEGG pathways were spliceosome, RNA transport, and DNA replication. In conclusion, the drug metabolism-related gene ADH1B and its interactive network play an essential role in the immune regulation and therapeutic response and maybe identified as promising therapeutic targets for OV patients.

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“…Neurons possess free ribosomes in their distal compartments and are thus capable of regulating protein synthesis locally and on-demand, using mRNA molecules that are trafficked to various subcellular locations and maintained in a dormant state unto specific stimulation ( Cajigas et al, 2012 ; Buxbaum et al, 2014 ; Zappulo et al, 2017 ; Glock et al, 2021 ). Since the translation of a single mRNA molecule can generate multiple proteins, localized protein synthesis is considered an energetically favorable mechanism over transport of individual proteins to distal axonal compartments, allowing for drastic alteration of the local proteome and subsequent rapid responses upon receipt of microenvironmental signaling ( Gasparski et al, 2022 ). On the other hand, the neuronal cytoskeleton, composed of actin filaments (filamentous actin or F-actin), neurofilaments, and microtubules (MTs), acts as a key regulator of crucial molecular and cellular events related to the establishment and maintenance of neuronal polarity, morphology, structural integrity, and plasticity ( Luo, 2002 ; Barnes and Polleux, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Local mRNA translation and cytoskeletal reorganization: Mechanisms that tune neuronal responses

Triantopoulou

Vidaki

2022

Front. Mol. Neurosci.

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Neurons are highly polarized cells with significantly long axonal and dendritic extensions that can reach distances up to hundreds of centimeters away from the cell bodies in higher vertebrates. Their successful formation, maintenance, and proper function highly depend on the coordination of intricate molecular networks that allow axons and dendrites to quickly process information, and respond to a continuous and diverse cascade of environmental stimuli, often without enough time for communication with the soma. Two seemingly unrelated processes, essential for these rapid responses, and thus neuronal homeostasis and plasticity, are local mRNA translation and cytoskeletal reorganization. The axonal cytoskeleton is characterized by high stability and great plasticity; two contradictory attributes that emerge from the powerful cytoskeletal rearrangement dynamics. Cytoskeletal reorganization is crucial during nervous system development and in adulthood, ensuring the establishment of proper neuronal shape and polarity, as well as regulating intracellular transport and synaptic functions. Local mRNA translation is another mechanism with a well-established role in the developing and adult nervous system. It is pivotal for axonal guidance and arborization, synaptic formation, and function and seems to be a key player in processes activated after neuronal damage. Perturbations in the regulatory pathways of local translation and cytoskeletal reorganization contribute to various pathologies with diverse clinical manifestations, ranging from intellectual disabilities (ID) to autism spectrum disorders (ASD) and schizophrenia (SCZ). Despite the fact that both processes are essential for the orchestration of pathways critical for proper axonal and dendritic function, the interplay between them remains elusive. Here we review our current knowledge on the molecular mechanisms and specific interaction networks that regulate and potentially coordinate these interconnected processes.

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Regulation and outcomes of localized RNA translation

Cited by 32 publications

References 150 publications

Bento: A toolkit for subcellular analysis of spatial transcriptomics data

Bento: A toolkit for subcellular analysis of spatial transcriptomics data

The Roles of Drug Metabolism-Related ADH1B in Immune Regulation and Therapeutic Response of Ovarian Cancer

Local mRNA translation and cytoskeletal reorganization: Mechanisms that tune neuronal responses

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