Correction to The transcript interactome of skeletal muscle RNA binding protein motif 3 (RBM3).
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PROVIDER: S-EPMC10603379 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Correction to The transcript interactome of skeletal muscle RNA binding protein motif 3 (RBM3).
Physiological reports 20231001 20
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Project description:Post-transcriptional regulation of gene expression represents a critical regulatory step in the production of a functional proteome. Elevated expression of post-transcriptional regulator RNA binding motif protein 3 (RBM3), an RNA binding protein in the cold-shock family, is positively correlated with skeletal muscle growth in adult mice. However, mechanisms through which RBM3 exerts its effects are largely unknown. The purpose of this study was to perform RNA immunoprecipitation followed by RNA sequencing (RIP-seq) and apply a network science approach to understand biological processes (BPs) most associated with RBM3-bound mRNAs. In addition, through nucleotide-sequence-scanning of enriched transcripts, we predicted the motif for skeletal muscle RBM3 binding. Gene set enrichment analysis followed by enrichment mapping of RBM3-bound transcripts (fold change >3; p.adj <0.01) revealed significant enrichment of BPs associated with "Contractile apparatus," "Translation initiation," and "Proteosome complex." Clusters were driven largely by enrichment of Myh1 (FC: 4.43), Eif4b (FC: 5.03), and Trim63 (FC: 5.84), respectively. Motif scanning of enriched sequences revealed a discrete 14 nucleotide-wide motif found most prominently at the junction between the protein coding region's termination sequence and the start of the 3' untranslated region (UTR; E-Value: 1.1 e-015 ). Proof of concept investigation of motif location along enriched transcripts Myh1 and Myl4 revealed 3' UTR binding, suggesting RBM3 involvement in transcript half-life regulation. Together, these results demonstrate the potential influence of RBM3 in reshaping the skeletal muscle proteome through post-transcriptional regulation of mRNAs crucial to muscle adaptations.
| S-EPMC9904958 | biostudies-literature
Project description:AimsHigh expression of the RNA-binding motif protein 3 (RBM3) correlates with improved prognosis in several major types of cancer. The aim of the present study was to examine the prognostic value of RBM3 protein and mRNA expression in non-small cell lung cancer (NSCLC).Methods and resultsImmunohistochemical expression of RBM3 was evaluated in surgically treated NSCLC from two independent patient populations (n = 213 and n = 306). Staining patterns were correlated with clinicopathological parameters, overall survival (OS), and recurrence-free interval (RFI). Cases with high nuclear RBM3 protein expression had a prolonged 5-year OS in both cohorts when analyzing adenocarcinomas separately (P = .02 and P = .01). RBM3 remained an independent prognostic factor for OS in multivariable analysis of cohort I (HR 0.44, 95% CI 0.21-0.90) and for RFI in cohort II (HR 0.38, 95% CI 0.22-0.74). In squamous cell carcinoma, there was instead an insignificant association to poor prognosis. Also, the expression levels of RBM3 mRNA were investigated in 2087 lung adenocarcinomas and 899 squamous cell carcinomas assembled from 13 and 8 public gene expression microarray datasets, respectively. The RBM3 mRNA levels were not clearly associated with patient outcome in either adenocarcinomas or squamous cell carcinomas.ConclusionsThe results from this study support that high protein expression of RBM3 is linked to improved outcome in lung adenocarcinoma.
| S-EPMC7402820 | biostudies-literature
Project description:BackgroundThe RNA-binding motif protein 3 (RBM3) has been shown to be up-regulated in several types of cancer, including prostate cancer (PCa), compared to normal tissues. Increased RBM3 nuclear expression has been linked to improved clinical outcomes.AimsGiven that RBM3 has been hypothesized to play a role in critical nuclear functions such as chromatin remodeling, DNA damage response, and other post-transcriptional processes, we sought to: (1) quantify RBM3 protein levels in archival PCa samples; (2) develop a nuclear morphometric model to determine if measures of RBM3 protein levels and nuclear features could be used to predict disease aggressiveness and biochemical recurrence.Methods & resultsThis study utilized two tissue microarrays (TMAs) stained for RBM3 that included 80 total cases of PCa stratified by Gleason score. A software-mediated image processing algorithm identified RBM3-positive cancerous nuclei in the TMA samples and calculated twenty-two features quantifying RBM3 expression and nuclear architecture. Multivariate logistic regression (MLR) modeling was performed to determine if RBM3 levels and nuclear structural changes could predict PCa aggressiveness and biochemical recurrence (BCR). Leave-one-out cross validation (LOOCV) was used to provide insight on how the predictive capabilities of the feature set might behave with respect to an independent patient cohort to address issues such as model overfitting. RBM3 expression was found to be significantly downregulated in highly aggressive GS ≥ 8 PCa samples compared to other Gleason scores (P < 0.0001) and significantly down-regulated in recurrent PCa samples compared to non-recurrent samples (P = 0.0377). An eleven-feature nuclear morphometric MLR model accurately identified aggressive PCa, yielding a receiver operating characteristic area under the curve (ROC-AUC) of 0.90 (P < 0.0001) in the raw data set and 0.77 (95% CI: 0.83-0.97) for LOOCV testing. The same eleven-feature model was then used to predict recurrence, yielding a ROC-AUC of 0.92 (P = 0.0004) in the raw data set and 0.76 (95% CI: 0.64-0.87) for LOOCV testing.ConclusionsThe RBM3 biomarker alone is a strong prognostic marker for the prediction of aggressive PCa and biochemical recurrence. Further, RBM3 appears to be down-regulated in aggressive and recurrent tumors.
| S-EPMC7316183 | biostudies-literature
Project description:BackgroundRNA binding protein motif (RBM3) is associated with radioresistance in nasopharyngeal carcinoma (NPC), and miR-383-5p was predicted to target the 3'-untranslated region (3'UTR) of RBM3 messenger RNA (mRNA). Our study aimed to investigate the role and the mechanisms of miR-383-5p targeting RBM3 in NPC cell proliferation and radioresistance (RR).MethodsThe expression of miR-383-5p was detected by Real-time quantitative PCR (qRT-PCR) between RS (Radiosensitivity) and RR (Radioresistance) NPC patient- tissue specimens and cell lines. Cell Counting Kit-8 (CCK-8) and Clonogenic survival assay were applied to analyze the effect of miR-383-5p on NPC cell proliferation and radioresistance. Possible downstream target of miR-383-5p in NPC cells, RBM3was evaluated by luciferase assay and qRT-PCR. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3 by rescue experiments. The effect of miR-383-5p on radiation-induced apoptosis was explored through Flow cytometric analysis and Western blotting. Western blotting was analyzed the molecular of RBM3-mediated Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) signaling pathways.ResultsThe expression of miR-383-5p was decreased in radioresistant NPC tissues and cells. miR-383-5p inhibited cell proliferation and radioresistance in CNE1/IR cells. We also observed that therapeutic administration of a miR-383-5p agomir dramatically sensitized NPC xenografts to radiation in a mouse model. Conversely, in the same xenograft model, administration of a miR-383-5p antagomir dramatically increased NPC resistance to radiation. miR-383-5p targeted the 3'UTR of RBM3. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3. Finally, we found that miR-383-5p increased radiation-induced apoptosis, activated JNK signaling, and inhibited ERK signaling.ConclusionsOur study revealed that miR-383-5p targeted the 3'UTR of RBM3 and contributed to the efficacy of NPC radiation therapy by altering the RBM3-mediated JNK and ERK signaling pathways.
| S-EPMC7867938 | biostudies-literature
Project description:RNA-binding proteins (RBPs) have important roles in transcription, pre-mRNA processing/transport, mRNA degradation, translation, and non-coding RNA processing, among others. RBPs that are expressed in response to cold stress, such as Cirp and Rbm3, could regulate RNA stability and translation in hibernating mammals that reduce their body temperatures from 37 °C to as low as 0-5 °C during torpor bouts. RBPs including Cirp, Rbm3, and stress-inducible HuR translocate from the nucleus to stabilize mRNAs in the cytoplasm, and thereby could regulate which mRNA transcripts are protected from degradation and are translated, versus stored, for future protein synthesis or degraded by nucleases during cell stress associated with metabolic rate depression. This is the first study to explore the transcriptional/translational regulation, and subcellular localization of cold-inducible RBPs in a model hibernator, the 13-lined ground squirrel (Ictidomys tridecemlineatus). Cirp protein levels were upregulated in liver, skeletal muscle, and brown adipose tissue throughout the torpor-arousal cycle whereas Rbm3 protein levels stayed constant or decreased, suggesting an important role for Cirp, but likely not Rbm3, in the hibernator stress response. Increased cytoplasmic localization of Cirp in liver and muscle and HuR in liver during torpor, but no changes in the relative levels of Rbm3 in the cytoplasm, emphasizes a role for Cirp and possibly HuR in regulating mRNA processing during torpor. This study informs our understanding of the natural adaptations that extreme animals use in the face of stress, and highlight natural stress response mediators that could be used to bolster cryoprotection of human organs donated for transplant.
| S-EPMC7591650 | biostudies-literature
Project description:Radioresistance is an important obstacle to nasopharyngeal carcinoma (NPC) therapy. In this study, we explored the role of RNA-binding motif protein 3 (RBM3) in the radioresistance of NPC and its underlying mechanism. We measured the expression of RBM3 in 20 clinical NPC tissues and in NPC cell lines. We found that RBM3 was upregulated in radioresistant NPC tissues and cells. Radioresistant NPC cells (CNE1/IR) and parental NPC cells (CNE1) were subjected to RBM3-shRNA knockdown and RBM3 overexpression, respectively. RBM3 depletion in CNE1/IR cells sensitized cells to radiotherapy, increased DNA damage, and accelerated the rate of apoptosis. In contrast, RBM3 overexpression in CNE1 cells significantly enhanced radioresistance and reduced the rate of apoptosis. Additionally, radioresistance conferred by RBM3 was attributed to the activation of the AKT/Bcl-2 signaling pathway and reduction of caspase 3. Inhibition of AKT signaling attenuated RBM3-mediated radioresistance. Furthermore, RBM3 directly interacted with PI3K subunit p85 in NPC cell lines. Altogether, our data demonstrate that RBM3 enhances radioresistance by inhibiting the apoptotic response to radiotherapy through the PI3K/AKT/Bcl-2 signaling pathway. RBM3 may serve as a novel factor for predicting radioresistance and as a molecular target in the treatment of NPC.
| S-EPMC6325530 | biostudies-literature
Project description:Muscular atrophy is a mortality risk factor that happens with disuse, chronic disease, and aging. Recovery from atrophy requires changes in several cell types including muscle fibers, and satellite and immune cells. Here we show that Zfp697/ZNF697 is a damage-induced regulator of muscle regeneration, during which its expression is transiently elevated. Conversely, sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Myofiber-specific Zfp697 ablation hinders the inflammatory and regenerative response to muscle injury, compromising functional recovery. We uncover Zfp697 as an essential interferon gamma mediator in muscle cells, interacting primarily with ncRNAs such as the pro-regenerative miR-206. In sum, we identify Zfp697 as an integrator of cell-cell communication necessary for tissue regeneration.One sentence summaryZfp697 is necessary for interferon gamma signaling and muscle regeneration.
| S-EPMC10312635 | biostudies-literature
Project description:Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and satellite and immune cells. Here, we show that the previously uncharacterized gene and protein Zfp697 is a damage-induced regulator of muscle remodeling. Zfp697/ZNF697 expression is transiently elevated during recovery from muscle atrophy or injury in mice and humans. Sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Notably, although Zfp697 is expressed in several cell types in skeletal muscle, myofiber-specific Zfp697 genetic ablation in mice is sufficient to hinder the inflammatory and regenerative response to muscle injury, compromising functional recovery. We show that Zfp697 is an essential mediator of the interferon gamma response in muscle cells and that it functions primarily as an RNA-interacting protein, with a very high number of miRNA targets. This work identifies Zfp697 as an integrator of cell-cell communication necessary for tissue remodeling and regeneration.
| S-EPMC11348326 | biostudies-literature
Project description:Neural stem cells (NSCs) reside physiologically in a hypoxic niche to maintain self-renewal and multipotency. Whereas mild hypoxia is known to promote NSC proliferation, severe hypoxia in pathological conditions exerts the reverse effect. The multi-functional RNA-binding protein RBM3 is abundant in NSCs and can be regulated by hypoxic exposure. Although RBM3 has been shown to accelerate cell growth in many cell types, whether and how it affects NSC proliferation in hypoxic environment remains largely unknown. In this study, we tested how RBM3 regulates cell proliferation under hypoxia in C17.2 mouse NSC cell line and in primary mouse NSCs from both the forebrain of postnatal day 0 (P0) mice and the subgranular zone (SGZ) of adult mice. Our results demonstrated that RBM3 expression was highly sensitive to hypoxia, and NSCs were arrested in G0/G1 phase by 5, 2.5, and 1% O2 treatment. When we overexpressed RBM3, hypoxia-induced cell cycle arrest in G0/G1 phase was relieved and more cell transit into S phase was observed. Furthermore, cell viability under hypoxia was also increased by RBM3. In contrast, in RBM3-depleted primary NSCs, less BrdU-incorporated cells were detected, indicating exacerbated cell cycle arrest in G1 to S phase transition. Instead, overexpressed RBM3 significantly increased proliferation ratio in primary NSCs. Our findings indicate RBM3 as a potential target to maintain the proliferation capacity of NSCs under hypoxia, which can be important in NSC-based therapies of acute brain injury and chronic neurodegenerative diseases.
| S-EPMC6881237 | biostudies-literature
Project description:BackgroundInadequate dietary protein intake causes adverse changes in the morphology and function of skeletal muscle. These changes may be reflected in early alterations in muscle messenger RNA levels.ObjectiveThis study assessed whether inadequate protein intake differentially affects skeletal muscle transcript concentrations and expression profiles in older adults.DesignTwenty-one older men and women (aged 55-80 y) consumed controlled diets that provided 1.2 g protein x kg(-1) x d(-1) (adequate protein) for 1 wk and then were randomly assigned to consume either 0.5 g protein x kg(-1) x d(-1) [inadequate protein (IP) group; n=11] or 1.2 g protein x kg(-1) x d(-1) (control group; n=10) for a second week. RNA was isolated from fasting-state vastus lateralis biopsy samples obtained at the end of each period, and transcript levels in the IP group were measured by using microarray analysis. Changes in selected transcript levels were confirmed by real-time polymerase chain reaction in both groups.ResultsAnalysis of variance showed 529 differentially expressed transcripts (P<0.05) after inadequate protein intake. Using the false discovery rate (FDR) correction to adjust for multiple comparisons, we observed that 85 transcripts were differentially expressed: 54 were up-regulated and 31 were down-regulated. The differentially expressed transcripts were in functional classes for immune, inflammatory, and stress responses (predominantly up-regulated); contraction, movement, and development (up-regulated); extracellular connective tissue (up-regulated); energy metabolism (down-regulated); protein synthesis (down-regulated); and proliferation (down-regulated). Diet-related differences in the expression of 9 transcripts were cross-validated by using real-time polymerase chain reaction.ConclusionThe results document changes in skeletal muscle transcript levels induced by short-term inadequate protein intakes in older humans that might precede adverse metabolic, functional, and structural events, including muscle wasting.
| S-EPMC2447912 | biostudies-literature