Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"Long non-coding RNA Snhg15 promotes preosteoblast proliferation by interacting with and stabilizing nucleolin","authors":"Jiaqi Zhu ,&nbsp;Lijuan Mo ,&nbsp;Mengying Li ,&nbsp;Yunlei Wang ,&nbsp;Gengming Zhang ,&nbsp;Zhendong Tao ,&nbsp;Xiaozhu Liao ,&nbsp;Mingyuan Du ,&nbsp;Hong He","doi":"10.1016/j.bbamcr.2024.119847","DOIUrl":"10.1016/j.bbamcr.2024.119847","url":null,"abstract":"<div><p>The proliferation and mineralization of preosteoblasts is crucial for bone formation and has attracted extensive attentions for decades. However, the roles of numerous long non-coding RNAs (lncRNAs) in preosteoblasts have not been fully determined. This study aimed to investigate the function of lncRNA <em>Snhg15</em> in preosteoblasts as well as the potential underlying mechanism. LncRNA <em>Snhg15</em> was dynamically expressed during preosteoblast proliferation and mineralization, and its transcripts were localized mainly in the cytoplasm. LncRNA <em>Snhg15</em> knockdown significantly inhibited the proliferation and mineralization of preosteoblasts in both a cellular model and a murine ectopic bone formation model. RNA-seq showed that lncRNA <em>Snhg15</em> knockdown downregulated multiple proliferation-related genes, and cell cycle deregulation was verified by flow cytometry. Mechanistically, we found that lncRNA <em>Snhg15</em> could bind to nucleolin (NCL), thereby block NCL ubiquitination and decrease its degradation. Furthermore, the overexpression of NCL in lncRNA <em>Snhg15</em>-knockdown preosteoblasts ameliorated GO/G1 phase cell cycle arrest. Moreover, experiments in an in situ bone formation model confirmed the negative effects of lncRNA <em>Snhg15</em> deficiency on bone formation. In conclusion, this study revealed an important regulatory role of lncRNA <em>Snhg15</em>/NCL complex in preosteoblast proliferation and may provide insights into the molecular mechanisms underlying bone formation.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119847"},"PeriodicalIF":4.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHRS2-induced SPHK1 downregulation contributes to the cell growth inhibition by Trichothecin in colorectal carcinoma","authors":"Huiwen Liu ,&nbsp;Xiang Li ,&nbsp;Wenbin Liu ,&nbsp;Chunhong Zhang ,&nbsp;Shuzhao Zhang ,&nbsp;Xinran Zhou ,&nbsp;Ann M. Bode ,&nbsp;Xiangjian Luo","doi":"10.1016/j.bbamcr.2024.119846","DOIUrl":"10.1016/j.bbamcr.2024.119846","url":null,"abstract":"<div><h3>Background</h3><div>Deregulation of lipid metabolism is one of the most prominent metabolic features in cancer. The activation of sphingolipid metabolic pathways affects the proliferation, invasion, angiogenesis, chemoresistance, and immune escape of tumors, including colorectal cancer (CRC). Dehydrogenase/reductase member 2 (DHRS2), which belongs to the short-chain dehydrogenase/reductase (SDR) family, has been reported to participate in the regulation of lipid metabolism and impact on cancer progression.</div><div>Trichothecin (TCN) is a sesquiterpenoid metabolite originating from an endophytic fungus of the herbal plant Maytenus hookeri Loes. Studies have shown that TCN exerts a broad-spectrum antitumor activity.</div></div><div><h3>Methods</h3><div>We evaluated the proliferative ability of CRC cells by CCK8 and colony formation assays. A metabolite profiling using liquid chromatography coupled with mass spectrometry (LC/MS) was adopted to identify the proximal metabolite changes linked to DHRS2 overexpression. RNA stability assay and RNA immunoprecipitation (RIP) experiments were applied to determine the post-transcriptional regulation of <em>SPHK1</em> expression by DHRS2. We used flow cytometry to detect changes in cell cycle and cell apoptosis of CRC cells in the absence or presence of TCN.</div></div><div><h3>Results</h3><div>We demonstrate that DHRS2 hampers the sphingosine kinases 1 (SPHK1)/sphingosine 1-phosphate (S1P) metabolic pathway to inhibit CRC cell growth. DHRS2 directly binds to <em>SPHK1</em> mRNA to accelerate its degradation in a post-transcriptionally regulatory manner. Moreover, we illustrate that SPHK1 downregulation induced by DHRS2 contributes to TCN-induced growth inhibition of CRC.</div></div><div><h3>Conclusions</h3><div>The present study provides a mechanistic connection among metabolic enzymes, metabolites, and the malignant progression of CRC. Moreover, TCN could be developed as a potential pharmacological tool against CRC by the induction of DHRS2 and targeting SPHK1/S1P metabolic pathway.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119846"},"PeriodicalIF":4.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WDR45-dependent impairment of cell cycle in fibroblasts of patients with beta propeller protein-associated neurodegeneration (BPAN)","authors":"Barbara Garavaglia ,&nbsp;Alessia Nasca ,&nbsp;Stefania Mitola ,&nbsp;Rosaria Ingrassia","doi":"10.1016/j.bbamcr.2024.119842","DOIUrl":"10.1016/j.bbamcr.2024.119842","url":null,"abstract":"<div><p>De novo mutations in the <em>WDR45</em> gene have been found in patients affected by Neurodegeneration with Brain Iron Accumulation type 5 (NBIA5 or BPAN), with Non-Transferrin Bound Iron (NTBI) accumulation in the basal ganglia and WDR45-dependent impairment of autophagy. Here we show the downregulation of TFEB and cell cycle impairment in BPAN primary fibroblasts. Noteworthy, TFEB overexpression rescued this impairment, depicting a novel WDR45-dependent cell cycle phenotype.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119842"},"PeriodicalIF":4.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRSF2 is essential for maintaining pancreatic beta-cell identity and regulating glucose homeostasis in mice","authors":"Xue You ,&nbsp;Qian Peng ,&nbsp;Wenju Qian ,&nbsp;Huimin Duan ,&nbsp;Zhiqin Xie ,&nbsp;Ying Feng","doi":"10.1016/j.bbamcr.2024.119845","DOIUrl":"10.1016/j.bbamcr.2024.119845","url":null,"abstract":"<div><p>Diabetes is characterized by decreased beta-cell mass and islet dysfunction. The splicing factor SRSF2 plays a crucial role in cell survival, yet its impact on pancreatic beta cell survival and glucose homeostasis remains unclear. We observed that the deletion of <em>Srsf2</em> specifically in beta cells led to time-dependent deterioration in glucose tolerance, impaired insulin secretion, decreased islet mass, an increased number of alpha cells, and the onset of diabetes by the age of 10 months in mice. Single-cell RNA sequencing (scRNA-seq) analyses revealed that, despite an increase in populations of unfolded protein response (UPR)-activated and undifferentiated beta cells within the SRSF2_KO group, there was a notable decrease in the expression of UPR-related and endoplasmic reticulum (ER)-related genes, accompanied by a loss of beta-cell identity. This suggests that beta cells have transitioned from an adaptive phase to a maladaptive phase in islets of 10-month-old SRSF2_KO mice. Further results demonstrated that deletion of SRSF2 caused decreased proliferation in beta cells within 3-month-old islets and Min6 cells. These findings underscore the essential role of SRSF2 in controlling beta-cell proliferation and preserving beta-cell function in mice.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119845"},"PeriodicalIF":4.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the functions of ACBD4/5-like proteins using a combined phylogenetic and experimental approach across model organisms","authors":"Suzan Kors ,&nbsp;Martin Schuster ,&nbsp;Daniel C. Maddison ,&nbsp;Sreedhar Kilaru ,&nbsp;Tina A. Schrader ,&nbsp;Joseph L. Costello ,&nbsp;Markus Islinger ,&nbsp;Gaynor A. Smith ,&nbsp;Michael Schrader","doi":"10.1016/j.bbamcr.2024.119843","DOIUrl":"10.1016/j.bbamcr.2024.119843","url":null,"abstract":"<div><div>Acyl-CoA binding domain-containing proteins (ACBDs) perform diverse but often uncharacterised functions linked to cellular lipid metabolism. Human ACBD4 and ACBD5 are closely related peroxisomal membrane proteins, involved in tethering of peroxisomes to the ER and capturing fatty acids for peroxisomal β-oxidation. ACBD5 deficiency causes neurological abnormalities including ataxia and white matter disease. Peroxisome-ER contacts depend on an ACBD4/5-FFAT motif, which interacts with ER-resident VAP proteins. As ACBD4/5-like proteins are present in most fungi and all animals, we combined phylogenetic analyses with experimental approaches to improve understanding of their evolution and functions. Notably, all vertebrates exhibit gene sequences for both ACBD4 and ACBD5, while invertebrates and fungi possess only a single ACBD4/5-like protein. Our analyses revealed alterations in domain structure and FFAT sequences, which help understanding functional diversification of ACBD4/5-like proteins. We show that the <em>Drosophila melanogaster</em> ACBD4/5-like protein possesses a functional FFAT motif to tether peroxisomes to the ER via Dm_Vap33. Depletion of Dm_Acbd4/5 caused peroxisome redistribution in wing neurons and reduced life expectancy. In contrast, the ACBD4/5-like protein of the filamentous fungus <em>Ustilago maydis</em> lacks a FFAT motif and does not interact with Um_Vap33. Loss of Um_Acbd4/5 resulted in an accumulation of peroxisomes and early endosomes at the hyphal tip. Moreover, lipid droplet numbers increased, and mitochondrial membrane potential declined, implying altered lipid homeostasis. Our findings reveal differences between tethering and metabolic functions of ACBD4/5-like proteins across evolution, improving our understanding of ACBD4/5 function in health and disease. The need for a unifying nomenclature for ACBD proteins is discussed.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119843"},"PeriodicalIF":4.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEDD4L-mediated RASGRP2 suppresses high-glucose and oxLDL-induced vascular endothelial cell dysfunctions by activating Rap1 and R-Ras","authors":"Guozhu Chen ,&nbsp;Yisong Pei ,&nbsp;Qiaoling Ye ,&nbsp;Zulong Xie ,&nbsp;Laxman Gyawali ,&nbsp;Xing Liang","doi":"10.1016/j.bbamcr.2024.119844","DOIUrl":"10.1016/j.bbamcr.2024.119844","url":null,"abstract":"<div><h3>Background</h3><div>Ras guanyl-releasing protein 2 (RASGRP2) is an important regulator mediating endothelial cell function. However, whether RASGRP2 mediates diabetes mellitus (DM)-related atherosclerosis (AS) progression by regulating endothelial cell functions is unknown.</div></div><div><h3>Methods</h3><div>Human cardiac microvascular endothelial cells (HCMECs) were treated with high-glucose (HG) and oxidized low-density lipoprotein (oxLDL). The expression of RASGRP2 and neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) was examined by quantitative real-time PCR and western blot (WB). Cell viability, apoptosis, migration, angiogenesis were detected by CCK8 assay, flow cytometry, transwell assay and tube formation assay. ROS production and cell permeability were tested to assess cell function. Rap1 and R-Ras protein levels were examined using WB. The interaction between RASGRP2 and NEDD4L was confirmed by Co-IP assay and ubiquitination assay. Exosomes were isolated from adipose-derived MSC (ADMSC)-transfected RASGRP2 overexpression vector, and then co-cultured with HG + oxLDL-induced HCMECs.</div></div><div><h3>Results</h3><div>RASGRP2 was lowly expressed in HG + oxLDL-induced HCMECs. RASGRP2 overexpression inhibited HG + oxLDL-induced HCMECs permeability, apoptosis and ROS production, while accelerated cell viability, migration and angiogenesis. NEDD4L could interact with RASGRP2 by ubiquitination, thus inhibiting RASGRP2 protein stability to degrade its expression. Functional experiments showed that NEDD4L knockdown suppressed HG + oxLDL-induced HCMECs dysfunction, while these effects were reversed by RASGRP2 downregulation. ADMSC-Exo overexpressed RASGRP2 could promote cell viability, migration and angiogenesis, while suppress permeability, apoptosis and ROS production in HG + oxLDL-induced HCMECs.</div></div><div><h3>Conclusion</h3><div>Our data showed that targeting NEDD4L/RASGRP2 axis or inducing RASGRP2-modified ADMSC-Exo might be the efficient strategy for alleviating DM-related AS.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119844"},"PeriodicalIF":4.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRSF3 suppresses RCC tumorigenesis and progression via regulating SP4 alternative splicing","authors":"Liuxu Zhang ,&nbsp;Hongning Zhang ,&nbsp;Yuangui Tang ,&nbsp;Chenyun Dai ,&nbsp;Junfang Zheng","doi":"10.1016/j.bbamcr.2024.119841","DOIUrl":"10.1016/j.bbamcr.2024.119841","url":null,"abstract":"<div><p>Abnormal alternative splicing (AS) caused by dysregulated expression of splicing factors plays a crucial role in tumorigenesis and progression. The serine/arginine-rich (SR) RNA-binding protein family is a major class of splicing factors regulating AS. However, their roles and mechanisms in renal cell carcinoma (RCC) development and progression are not fully understood. Here, we found that SR splicing factor 3 (SRSF3) was an important splicing factor affecting RCC progression. SRSF3 was downregulated in RCC tissues and its low level was associated with decreased overall survival time of RCC patients. SRSF3 overexpression suppressed RCC cell malignancy. Mechanistically, the binding of SRSF3 to <em>SP4</em> exon 3 led to the inclusion of <em>SP4</em> exon 3 and the increase of long SP4 isoform (L-SP4) level in RCC cells. L-SP4, but not S-SP4 overexpression suppressed RCC cell malignancy. Meanwhile, L-SP4 participated in SRSF3-mediated anti-proliferation by transcriptionally promoting SMAD4 expression. Taken together, our findings provide new insights into the anticancer mechanism of SRSF3, suggesting that SRSF3 may serve as a novel potential therapeutic target for RCC.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119841"},"PeriodicalIF":4.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPP1R14B-mediated phosphorylation enhances protein stability of RPS6KA1 to promote hepatocellular carcinoma tumorigenesis","authors":"Nana Zhou ,&nbsp;Chaoqin Guo ,&nbsp;Jingyang Du ,&nbsp;Qiuran Xu ,&nbsp;Juejiashan Li ,&nbsp;Dongsheng Huang ,&nbsp;Xiaoliang Zheng ,&nbsp;Linglan Tu","doi":"10.1016/j.bbamcr.2024.119840","DOIUrl":"10.1016/j.bbamcr.2024.119840","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide with a poor clinical prognosis. Protein phosphatase 1 regulatory subunit 14B (PPP1R14B) is an unidentified protein phosphatase 1 regulatory subunit that is associated with the occurrence and development of various cancers. Recently, PPP1R14B was found to contribute to paclitaxel resistance and cell progression in triple-negative breast cancer; however, the role of PPP1R14B in HCC is unknown. Here, we found that PPP1R14B was highly expressed in HCC tissues, which suggested a poor prognosis. Knockdown of PPP1R14B significantly inhibited the survival and tumorigenic ability of HCC cells, while overexpression of PPP1R14B had the opposite effects. Mechanistically, Ribosomal Protein S6 Kinase type 1(RPS6KA1) was identified as the target gene of PPP1R14B. PPP1R14B maintained the stability and phosphorylation of RPS6KA1, and positively regulated activation of the AKT/NF-κB pathway. Importantly, PPP1R14B-deficient tumor suppression could be partially restored by wild-type but not phosphorylated mutant RPS6KA1. Taken together, these findings shed light on the function and mechanism of PPP1R14B in HCC progression, indicating PPP1R14B is a promising molecular target for the treatment of HCC.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119840"},"PeriodicalIF":4.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001836/pdfft?md5=c1a248f317586164f50cc672d12927ac&pid=1-s2.0-S0167488924001836-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NHEJ is promoted by the phosphorylation and phosphatase activity of PTEN via regulation of DNA-PKcs","authors":"Sougata Ghosh Chowdhury ,&nbsp;Sandip Misra ,&nbsp;Ginia Ghosh ,&nbsp;Ananda Mukherjee ,&nbsp;Priyanka Gopi ,&nbsp;Prateek Pandya ,&nbsp;Md. Maidul Islam ,&nbsp;Parimal Karmakar","doi":"10.1016/j.bbamcr.2024.119828","DOIUrl":"10.1016/j.bbamcr.2024.119828","url":null,"abstract":"<div><p>DNA double-strand breaks (DSBs) are considered one of the most harmful forms of DNA damage. These DSBs are repaired through non-homologous end joining (NHEJ) and homologous recombination (HR) pathways and defects in these processes can lead to genomic instability and promote tumorigenesis. Phosphatase and Tensin homolog (PTEN) are crucial in HR repair. However, its involvement in the NHEJ repair pathway has remained elusive. In this study, we investigate the function of epigenetic regulation of PTEN in the NHEJ repair pathway. Our findings indicate that both the phosphorylation and phosphatase activity of PTEN are required for efficient NHEJ-mediated DSB repair. During the DNA damage response, we observed a reduced expression and chromatin attachment of the key NHEJ proteins, including Ku70/80, DNA-PKcs, XRCC4, and XLF, in PTEN-null cells. This reduction was attributed to the instability of these NHEJ proteins, as confirmed by our protein half-life assay. We have demonstrated that the DNA-PKcs inhibitor, NU7026, suppresses the DNA damage-induced phosphorylation of the C-terminal of PTEN. Thus, our study indicates that PTEN could be a target of DNA-PKcs. Protein-protein docking analysis also shows that PTEN interacts with the C-terminal region of DNA-PKcs. PTEN null cells exhibit compromised DNA-PKcs foci after DNA damage as it is in a hyper-phosphorylated state. Phospho-PTEN assists in recruiting DNA-PKcs on the DNA damage site by maintaining its hypo-phosphorylated state which also depends on its phosphatase activity. Therefore, after DNA damage, crosstalk between PTEN and DNA-PKcs modulates the NHEJ pathway. Thus, during DNA damage, PTEN gets phosphorylated directly or indirectly by DNA-PKcs and attaches to chromatin, resulting in the dephosphorylation of DNA-PKcs and subsequently recruitment of other NHEJ factors on chromatin occurs for efficient execution of the NHEJ pathway. Thus, our research provides a molecular understanding of the epigenetic regulation of PTEN and its significant role in controlling the NHEJ pathway.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119828"},"PeriodicalIF":4.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal activation affects the organization and protein composition of the nuclear speckles","authors":"Andrzej Antoni Szczepankiewicz ,&nbsp;Kamil Parobczak ,&nbsp;Monika Zaręba-Kozioł ,&nbsp;Błażej Ruszczycki ,&nbsp;Monika Bijata ,&nbsp;Paweł Trzaskoma ,&nbsp;Grzegorz Hajnowski ,&nbsp;Dagmara Holm-Kaczmarek ,&nbsp;Jakub Włodarczyk ,&nbsp;Hanna Sas-Nowosielska ,&nbsp;Grzegorz Marek Wilczyński ,&nbsp;Maria Jolanta Rędowicz ,&nbsp;Adriana Magalska","doi":"10.1016/j.bbamcr.2024.119829","DOIUrl":"10.1016/j.bbamcr.2024.119829","url":null,"abstract":"<div><p>Nuclear speckles, also known as interchromatin granule clusters (IGCs), are subnuclear domains highly enriched in proteins involved in transcription and mRNA metabolism and, until recently, have been regarded primarily as their storage and modification hubs. However, several recent studies on non-neuronal cell types indicate that nuclear speckles may directly contribute to gene expression as some of the active genes have been shown to associate with these structures.</p><p>Neuronal activity is one of the key transcriptional regulators and may lead to the rearrangement of some nuclear bodies. Notably, the impact of neuronal activation on IGC/nuclear speckles organization and function remains unexplored. To address this research gap, we examined whether and how neuronal stimulation affects the organization of these bodies in granular neurons from the rat hippocampal formation. Our findings demonstrate that neuronal stimulation induces morphological and proteomic remodelling of the nuclear speckles under both <em>in vitro</em> and <em>in vivo</em> conditions. Importantly, these changes are not associated with cellular stress or cell death but are dependent on transcription and splicing.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119829"},"PeriodicalIF":4.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001721/pdfft?md5=531bf475ffb59aed7ac2dcaedf185d6f&pid=1-s2.0-S0167488924001721-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}