Coordination of RNA Processing Regulation by Signal Transduction Pathways

Ruta, Veronica; Pagliarini, Vittoria; Sette, Claudio

doi:10.3390/biom11101475

Cited by 14 publications

(8 citation statements)

References 241 publications

(387 reference statements)

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“…Namely, the activity of both the core spliceosomal components and accessory splicing factors is modulated by their reversible phosphorylation [ 14 ]. In turn, the subunits of protein kinases and phosphatases themselves undergo extensive AS at a transcript processing level followed by (de)phosphorylation markup, rendering the highly tuned interaction of both processes in phosphorylation-mediated signal transduction cascades [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts

Babenko

Redina

Smagin

et al. 2023

Genes

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Both aggressive and aggression-deprived (AD) individuals represent pathological cases extensively studied in psychiatry and substance abuse disciplines. We employed the animal model of chronic social conflicts curated in our laboratory for over 30 years. In the study, we pursued the task of evaluation of the key events in the dorsal striatum transcriptomes of aggression-experienced mice and AD species, as compared with the controls, using RNA-seq profiling. We evaluated the alternative splicing-mediated transcriptome dynamics based on the RNA-seq data. We confined our attention to the exon skipping (ES) events as the major AS type for animals. We report the concurrent posttranscriptional and posttranslational regulation of the ES events observed in the phosphorylation cycles (in phosphoproteins and their targets) in the neuron-specific genes of the striatum. Strikingly, we found that major neurospecific splicing factors (Nova1, Ptbp1, 2, Mbnl1, 2, and Sam68) related to the alternative splicing regulation of cAMP genes (Darpp-32, Grin1, Ptpn5, Ppp3ca, Pde10a, Prkaca, Psd95, and Adora1) are upregulated specifically in aggressive individuals as compared with the controls and specifically AD animals, assuming intense switching between isoforms in the cAMP-mediated (de)phosphorylation signaling cascade. We found that the coding alternative splicing events were mostly attributed to synaptic plasticity and neural development-related proteins, while the nonsense-mediated decay-associated splicing events are mostly attributed to the mRNA processing of genes, including the spliceosome and splicing factors. In addition, considering the gene families, the transporter (Slc) gene family manifested most of the ES events. We found out that the major molecular systems employing AS for their plasticity are the ‘spliceosome’, ‘chromatin rearrangement complex’, ‘synapse’, and ‘neural development/axonogenesis’ GO categories. Finally, we state that approximately 35% of the exon skipping variants in gene coding regions manifest the noncoding variants subject to nonsense-mediated decay, employed as a homeostasis-mediated expression regulation layer and often associated with the corresponding gene expression alteration.

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Section: Introductionmentioning

confidence: 99%

Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts

Babenko

Redina

Smagin

et al. 2023

Genes

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“…Acetyl-CoA is a central metabolite involved in several cellular processes, including energy production, lipid synthesis, and the production of certain neurotransmitters [ 89 , 90 ]. mRNA splicing removes introns, connects exons, and generates mature mRNA molecules ready for translation, and is a fundamental process in eukaryotic gene expression [ 91 , 92 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages

Wu,

Rau,

et al. 2024

Biomedicines

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Circulating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequencing was used to profile the long non-coding RNA expression in primary cultured macrophages treated with exosomes obtained from the blood of septic C57BL/6 mice, and it was discovered that the nuclear factor-kappa B (NF-κB)/miR-17-92a-1 cluster host gene (MIR17HG) pathways were activated in the macrophages. The inhibition of MIR17HG expression by RNA interference resulted in significantly decreased cell viability. RNA pull-down assays of MIR17HG revealed that ten protein targets bind to MIR17HG. Interaction networks of proteins pulled down by MIR17HG were constructed using GeneMANIA, and their functions were mainly involved in ribonucleoprotein granules, type I interferons, the regulation of organelle assembly, the biosynthesis of acetyl coenzyme A, as a signal transducer and activator of transcription (STAT) protein phosphorylation, and mRNA splicing. Furthermore, RNA interference inhibited MIR17HG expression, resulting in significantly decreased cell survival. In conclusion, this work discovered considerable MIR17HG overexpression in macrophages treated with circulating exosomes from sepsis-affected animals. This study’s findings assist us in comprehending the role of exosomes in modulating inflammatory responses and mediating pathogenic pathways in macrophages during sepsis.

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“…Why Msy2 is downregulated in Ube2i Zp3-cre+ remains to be determined. RNA binding proteins (RBP) are also targets of SUMOylation or contain SUMO-interacting motifs ( 60, 61 ), however, RBP SUMO-targets in oocyte biology remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

The E2 SUMO-conjugating enzyme UBE2I coordinates the oocyte and zygotic transcriptional programs

Briley

Ahmed

Jiang

et al. 2022

Preprint

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In mammals, meiotically competent oocytes develop cyclically during ovarian folliculogenesis. During folliculogenesis, prophase I arrested oocytes are transcriptionally active, producing and storing transcripts required for their growth and for early stages of embryogenesis prior to the maternal to zygotic transition. Defective oocyte development during folliculogenesis leads to meiotic defects, aneuploidy, follicular atresia, or non-viable embryos. Here we generated a novel oocyte-specific knockout of the SUMO E2 ligase, Ube2i, using Zp3-cre to test its function during folliculogenesis. Ube2i Zp3-cre+ female mice are sterile with oocytes that arrest in meiosis I with defective spindles and chromosome alignment. Fully grown mutant oocytes abnormally maintain transcription but downregulate maternal effect genes and prematurely activate the zygotic transcriptional program. Thus, this work uncovers UBE2i as a novel orchestrator of chromatin and transcriptional regulation in mouse oocytes.

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Coordination of RNA Processing Regulation by Signal Transduction Pathways

Cited by 14 publications

References 241 publications

Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts

Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts

Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages

The E2 SUMO-conjugating enzyme UBE2I coordinates the oocyte and zygotic transcriptional programs

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