Life Science Alliance最新文献_第2页

Identification of TNFAIP2 as a unique cellular regulator of CSF-1 receptor activation. 鉴定TNFAIP2作为CSF-1受体活化的独特细胞调节剂。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-12 Print Date: 2025-05-01 DOI: 10.26508/lsa.202403032

Randa A Abdelnaser, Masateru Hiyoshi, Naofumi Takahashi, Youssef M Eltalkhawy, Hidenobu Mizuno, Shunsuke Kimura, Koji Hase, Hiroshi Ohno, Kazuaki Monde, Akira Ono, Shinya Suzu

{"title":"Identification of TNFAIP2 as a unique cellular regulator of CSF-1 receptor activation.","authors":"Randa A Abdelnaser, Masateru Hiyoshi, Naofumi Takahashi, Youssef M Eltalkhawy, Hidenobu Mizuno, Shunsuke Kimura, Koji Hase, Hiroshi Ohno, Kazuaki Monde, Akira Ono, Shinya Suzu","doi":"10.26508/lsa.202403032","DOIUrl":"10.26508/lsa.202403032","url":null,"abstract":"The receptor of CSF-1 (CSF1R) encoding tyrosine kinase is essential for tissue macrophage development, and the therapeutic target for many tumors. However, it is not completely understood how CSF1R activation is regulated. Here, we identify the cellular protein TNF-α-induced protein 2 (TNFAIP2) as a unique regulator of CSF1R. CSF1R forms large aggregates in macrophages via unknown mechanisms. The inhibition or knockdown of TNFAIP2 reduced CSF1R aggregate formation and functional response of macrophages to CSF-1, which was consistent with reduced CSF1R activation after CSF-1 stimulation. When expressed in 293 cells, TNFAIP2 augmented CSF1R aggregate formation and CSF-1-induced CSF1R activation. CSF1R and TNFAIP2 bind the cellular phosphatidylinositol 4,5-bisphosphate (PIP2). The removal of the PIP2-binding motif of CSF1R or TNFAIP2, or the depletion of cellular PIP2 reduced CSF1R aggregate formation. Moreover, TNFAIP2 altered the cellular distribution of PIP2. Because CSF-1-induced dimerization of CSF1R is critical for its activation, our findings suggest that TNFAIP2 augments CSF1R aggregate formation via PIP2, which brings CSF1R monomers close to each other and enables the efficient dimerization and activation of CSF1R in response to CSF-1.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408792","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}

引用次数: 0

Canonical and non-canonical PRC1 differentially contribute to regulation of neural stem cell fate. 规范和非规范PRC1对神经干细胞命运的调节有差异。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-11 Print Date: 2025-04-01 DOI: 10.26508/lsa.202403006

Janine Hoffmann, Theresa M Schütze, Annika Kolodziejczyk, Karolin Küster, Annekathrin Kränkel, Susanne Reinhardt, Razvan P Derihaci, Cahit Birdir, Pauline Wimberger, Haruhiko Koseki, Mareike Albert

{"title":"Canonical and non-canonical PRC1 differentially contribute to regulation of neural stem cell fate.","authors":"Janine Hoffmann, Theresa M Schütze, Annika Kolodziejczyk, Karolin Küster, Annekathrin Kränkel, Susanne Reinhardt, Razvan P Derihaci, Cahit Birdir, Pauline Wimberger, Haruhiko Koseki, Mareike Albert","doi":"10.26508/lsa.202403006","DOIUrl":"10.26508/lsa.202403006","url":null,"abstract":"Neocortex development is characterized by sequential phases of neural progenitor cell (NPC) expansion, neurogenesis, and gliogenesis. Polycomb-mediated epigenetic mechanisms are known to play important roles in regulating the lineage potential of NPCs during development. The composition of Polycomb repressive complex 1 (PRC1) is highly diverse in mammals and was hypothesized to contribute to context-specific regulation of cell fate. Here, we have performed a side-by-side comparison of the role of canonical PRC1.2/1.4 and non-canonical PRC1.3/1.5, all of which are expressed in the developing neocortex, in NSC proliferation and differentiation. We found that the deletion of Pcgf2/4 in NSCs led to a strong reduction in proliferation and to altered lineage fate, both during the neurogenic and gliogenic phase, whereas Pcgf3/5 played a minor role. Mechanistically, genes encoding stem cell and neurogenic factors were bound by PRC1 and differentially expressed upon Pcgf2/4 deletion. Thus, rather than different PRC1 subcomplexes contributing to different phases of neural development, we found that canonical PRC1 played a more significant role in NSC regulation during proliferative, neurogenic, and gliogenic phases compared with non-canonical PRC1.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399443","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}

引用次数: 0

A biallelic variant in GORASP1 causes a novel Golgipathy with glycosylation and mitotic defects. GORASP1的双等位基因变异导致一种具有糖基化和有丝分裂缺陷的新型Golgipathy。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-11 Print Date: 2025-04-01 DOI: 10.26508/lsa.202403065

Sophie Lebon, Arnaud Bruneel, Séverine Drunat, Alexandra Albert, Zsolt Csaba, Monique Elmaleh, Alexandra Ntorkou, Yann Ténier, François Fenaille, Pierre Gressens, Sandrine Passemard, Odile Boespflug-Tanguy, Imen Dorboz, Vincent El Ghouzzi

{"title":"A biallelic variant in GORASP1 causes a novel Golgipathy with glycosylation and mitotic defects.","authors":"Sophie Lebon, Arnaud Bruneel, Séverine Drunat, Alexandra Albert, Zsolt Csaba, Monique Elmaleh, Alexandra Ntorkou, Yann Ténier, François Fenaille, Pierre Gressens, Sandrine Passemard, Odile Boespflug-Tanguy, Imen Dorboz, Vincent El Ghouzzi","doi":"10.26508/lsa.202403065","DOIUrl":"10.26508/lsa.202403065","url":null,"abstract":"GRASP65 is a Golgi-associated peripheral protein encoded by the GORASP1 gene and required for Golgi cisternal stacking in vitro. A key role of GRASP65 in the regulation of cell division has also been suggested. However, depletion of GRASP65 in mice has little effect on the Golgi structure and the gene has not been associated with any human phenotype to date. Here, we report the identification of the first human pathogenic variant of GORASP1 (c.1170_1171del; p.Asp390Glufs*18) in a patient combining a neurodevelopmental disorder with neurosensory, neuromuscular, and skeletal abnormalities. Functional analysis revealed that the variant leads to a total absence of GRASP65. The structure of the Golgi apparatus did not show fragmentation, but glycosylation anomalies such as hyposialylation were detected. Mitosis analyses revealed an excess of prometaphases and metaphases with polar chromosomes, suggesting a delay in the cell cycle. These phenotypes were recapitulated in RPE cells in which a similar mutation was introduced by CRISPR/Cas9. These results indicate that loss of GRASP65 in humans causes a novel Golgipathy associated with defects in glycosylation and mitotic progression.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399440","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}

引用次数: 0

Screening of homing and tissue-penetrating peptides by microdialysis and in vivo phage display. 通过微透析和体内噬菌体展示筛选归巢肽和穿透组织肽。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-11 Print Date: 2025-05-01 DOI: 10.26508/lsa.202201490

Toini Pemmari, Stuart Prince, Niklas Wiss, Kuldar Kõiv, Ulrike May, Tarmo Mölder, Aleksander Sudakov, Fernanda Munoz Caro, Soili Lehtonen, Hannele Uusitalo-Järvinen, Tambet Teesalu, Tero Ah Järvinen

{"title":"Screening of homing and tissue-penetrating peptides by microdialysis and in vivo phage display.","authors":"Toini Pemmari, Stuart Prince, Niklas Wiss, Kuldar Kõiv, Ulrike May, Tarmo Mölder, Aleksander Sudakov, Fernanda Munoz Caro, Soili Lehtonen, Hannele Uusitalo-Järvinen, Tambet Teesalu, Tero Ah Järvinen","doi":"10.26508/lsa.202201490","DOIUrl":"10.26508/lsa.202201490","url":null,"abstract":"In vivo phage display is a method used for identification of organ- or disease-specific vascular homing peptides for targeted delivery of pharmaceutics. It is agnostic as to the nature and identity of the target molecules. The current in vivo biopanning lacks inbuilt mechanisms to select for peptides capable of vascular homing that would also be capable of tissue penetration to reach therapeutically relevant cells in the tissue parenchyma. Here, we combined in vivo phage display with microdialysis-based parenchymal recovery and high-throughput sequencing to select for peptides that, besides vascular homing, facilitate extravasation and tissue penetration. We first demonstrated in skin wounds that the method can selectively separate known homing peptides from those with additional tissue-penetrating ability. Screening of a naïve peptide library identifies peptides that home and extravasate to extravascular granulation tissue in vascularized and diabetic wounds and cross blood-retina barrier in retinopathy. Our work suggests that in vivo phage display combined with microdialysis can be used for the discovery of vascular homing peptides capable of extravasation and tissue penetration.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399383","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}

引用次数: 0

FGF7 as an essential mediator for the onset of ankylosing enthesitis related to psoriatic dermatitis. FGF7作为与银屑病皮炎相关的强直性全身炎发病的重要介质。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-07 Print Date: 2025-04-01 DOI: 10.26508/lsa.202403073

Shin Ebihara, Yuji Owada, Masao Ono

引用次数: 0

PICH impacts the spindle assembly checkpoint via its DNA translocase and SUMO-interaction activities. PICH通过其DNA转位酶和sumo相互作用活动影响纺锤体组装检查点。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-07 Print Date: 2025-04-01 DOI: 10.26508/lsa.202403140

Bunu Lama, Hyewon Park, Anita Saraf, Victoria Hassebroek, Daniel Keifenheim, Tomoko Saito-Fujita, Noriko Saitoh, Vasilisa Aksenova, Alexei Arnaoutov, Mary Dasso, Duncan J Clarke, Yoshiaki Azuma

{"title":"PICH impacts the spindle assembly checkpoint via its DNA translocase and SUMO-interaction activities.","authors":"Bunu Lama, Hyewon Park, Anita Saraf, Victoria Hassebroek, Daniel Keifenheim, Tomoko Saito-Fujita, Noriko Saitoh, Vasilisa Aksenova, Alexei Arnaoutov, Mary Dasso, Duncan J Clarke, Yoshiaki Azuma","doi":"10.26508/lsa.202403140","DOIUrl":"10.26508/lsa.202403140","url":null,"abstract":"Either inhibiting or stabilizing SUMOylation in mitosis causes defects in chromosome segregation, suggesting that dynamic mitotic SUMOylation of proteins is critical to maintain integrity of the genome. Polo-like kinase 1-interacting checkpoint helicase (PICH), a mitotic chromatin remodeling enzyme, interacts with SUMOylated chromosomal proteins via three SUMO-interacting motifs (SIMs) to control their association with chromosomes. Using cell lines with conditional PICH depletion/PICH replacement, we revealed mitotic defects associated with compromised PICH functions toward SUMOylated chromosomal proteins. Defects in either remodeling activity or SIMs of PICH delayed mitotic progression caused by activation of the spindle assembly checkpoint (SAC) indicated by extended duration of Mad1 foci at centromeres. Proteomics analysis of chromosomal SUMOylated proteins whose abundance is controlled by PICH activity identified candidate proteins to explain the SAC activation phenotype. Among the identified candidates, Bub1 kinetochore abundance is increased upon loss of PICH. Our results demonstrated a novel relationship between PICH and the SAC, where PICH directly or indirectly affects Bub1 association at the kinetochore and impacts SAC activity to control mitosis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370743","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}

引用次数: 0

Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos. Trim71-KO胚胎的原始红细胞功能受损和血管发育缺陷。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-05 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402956

Tobias Beckröge, Bettina Jux, Hannah Seifert, Hannah Theobald, Elena De Domenico, Stefan Paulusch, Marc Beyer, Andreas Schlitzer, Elvira Mass, Waldemar Kolanus

{"title":"Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos.","authors":"Tobias Beckröge, Bettina Jux, Hannah Seifert, Hannah Theobald, Elena De Domenico, Stefan Paulusch, Marc Beyer, Andreas Schlitzer, Elvira Mass, Waldemar Kolanus","doi":"10.26508/lsa.202402956","DOIUrl":"10.26508/lsa.202402956","url":null,"abstract":"The transition of an embryo from gastrulation to organogenesis requires precisely coordinated changes in gene expression, but the underlying mechanisms remain unclear. The RNA-binding protein Trim71 is essential for development and serves as a potent regulator of post-transcriptional gene expression. Here, we show that global deficiency of Trim71 induces severe defects in mesoderm-derived cells at the onset of organogenesis. Murine Trim71-KO embryos displayed impaired primitive erythropoiesis, yolk sac vasculature, heart function, and circulation, explaining the embryonic lethality of these mice. Tie2 Cre Trim71 conditional knockout did not induce strong defects, showing that Trim71 expression in endothelial cells and their immediate progenitors is dispensable for embryonic survival. scRNA-seq of E7.5 global Trim71-KO embryos revealed that transcriptomic changes arise already at gastrulation, showing a strong up-regulation of the mesodermal pioneer transcription factor Eomes. We identify Eomes as a direct target of Trim71-mediated mRNA repression via the NHL domain, demonstrating a functional link between these important regulatory genes. Taken together, our data suggest that Trim71-dependent control of gene expression at gastrulation establishes a framework for proper development during organogenesis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255324","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}

引用次数: 0

Sustained induction of autophagy enhances survival during prolonged starvation in newt cells. 持续诱导自噬可提高蝾螈细胞在长期饥饿期间的存活率。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-04 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402772

Md Mahmudul Hasan, Shinji Goto, Reiko Sekiya, Toshinori Hayashi, Tao-Sheng Li, Tsuyoshi Kawabata

{"title":"Sustained induction of autophagy enhances survival during prolonged starvation in newt cells.","authors":"Md Mahmudul Hasan, Shinji Goto, Reiko Sekiya, Toshinori Hayashi, Tao-Sheng Li, Tsuyoshi Kawabata","doi":"10.26508/lsa.202402772","DOIUrl":"10.26508/lsa.202402772","url":null,"abstract":"Salamanders demonstrate exceptional resistance to starvation, allowing them to endure extended periods without food in their natural habitats. Although autophagy, a process involving evolutionarily conserved proteins, promotes survival during food scarcity, the specific mechanism by which it contributes to the extreme starvation resistance in newt cells remains unexplored. Our study, using the newt species Pleurodeles waltl, reveals that newt primary fibroblasts maintain constant autophagy activation during prolonged cellular starvation. Unlike normal mammalian fibroblasts, where autophagosome formation increases during acute starvation but returns to baseline levels after extended periods, newt cells maintain elevated autophagosome numbers even 4 d after autophagy initiation, surpassing levels observed in nutrient-rich conditions. Unique P. waltl mTOR orthologs show reduced lysosomal localization compared with mammalian cells in both nutrient-rich and starved states. However, newt cells exhibit dephosphorylation of mTOR substrates under starvation conditions, similar to mammalian cells. These observations suggest that newts may have evolved a distinctive system to balance seemingly conflicting factors: high regenerative capacity and autophagy-mediated survival during starvation.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189765","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}

引用次数: 0

Unconventional receptor functions and location-biased signaling of the lactate GPCR in the nucleus. 细胞核中乳酸GPCR的非常规受体功能和位置偏向信号传导。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-04 Print Date: 2025-04-01 DOI: 10.26508/lsa.202503226

Mohammad Ali Mohammad Nezhady, Gael Cagnone, Emmanuel Bajon, Prabhas Chaudhari, Monir Modaresinejad, Pierre Hardy, Damien Maggiorani, Christiane Quiniou, Jean-Sébastien Joyal, Christian Beauséjour, Sylvain Chemtob

{"title":"Unconventional receptor functions and location-biased signaling of the lactate GPCR in the nucleus.","authors":"Mohammad Ali Mohammad Nezhady, Gael Cagnone, Emmanuel Bajon, Prabhas Chaudhari, Monir Modaresinejad, Pierre Hardy, Damien Maggiorani, Christiane Quiniou, Jean-Sébastien Joyal, Christian Beauséjour, Sylvain Chemtob","doi":"10.26508/lsa.202503226","DOIUrl":"10.26508/lsa.202503226","url":null,"abstract":"G-protein-coupled receptors (GPCRs) are virtually involved in every physiological process. However, mechanisms for their ability to regulate a vast array of different processes remain elusive. An unconventional functional modality could at least in part account for such diverse involvements but has yet to be explored. We found HCAR1, a multifunctional lactate GPCR, to localize at the nucleus and therein capable of initiating location-biased signaling notably nuclear-ERK and AKT. We discovered that nuclear HCAR1 (N-HCAR1) is directly involved in regulating diverse processes. Specifically, N-HCAR1 binds to protein complexes that are involved in promoting protein translation, ribosomal biogenesis, and DNA-damage repair. N-HCAR1 also interacts with chromatin remodelers to directly regulate gene expression. We show that N-HCAR1 displays a broader transcriptomic signature than its plasma membrane counterpart. Interestingly, exclusion of HCAR1 from the nucleus has the same effect as its complete cellular depletion on tumor growth and metastasis in vivo. These results reveal noncanonical functions for a cell nucleus-localized GPCR that are distinct from traditional receptor modalities and through which HCAR1 can participate in regulating various cellular processes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189768","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}

引用次数: 0

Assessment of PRMT6-dependent alternative splicing in pluripotent and differentiating NT2/D1 cells. 多能和分化NT2/D1细胞中prmt6依赖性选择性剪接的评估。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-03 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402946

Matthias Eudenbach, Jonas Busam, Caroline Bouchard, Oliver Rossbach, Kathi Zarnack, Uta-Maria Bauer

{"title":"Assessment of PRMT6-dependent alternative splicing in pluripotent and differentiating NT2/D1 cells.","authors":"Matthias Eudenbach, Jonas Busam, Caroline Bouchard, Oliver Rossbach, Kathi Zarnack, Uta-Maria Bauer","doi":"10.26508/lsa.202402946","DOIUrl":"10.26508/lsa.202402946","url":null,"abstract":"Protein arginine methyltransferase 6 (PRMT6) is a well-characterized epigenetic regulator that methylates histone H3 at arginine 2 (H3R2me2a) in both promoter and enhancer regions, thereby modulating transcriptional initiation. We report here that PRMT6 also regulates gene expression at the post-transcriptional level in the neural pluripotent state and during neuronal differentiation of NT2/D1 cells. PRMT6 knockout causes widespread alternative splicing changes in NT2/D1 cells, most frequently cassette exon alterations. Most of the PRMT6-dependent splicing targets are not transcriptionally affected by the enzyme and regulated in an H3R2me2a-independent manner. However, for a small subset of splicing events, the PRMT6-mediated deposition of H3R2me2a overlaps with the splice site, suggesting a potential dual function in both transcriptional and co-/post-transcriptional regulation. The splicing targets of PRMT6 include ribosomal proteins, splicing factors, and chromatin-modifying enzymes such as PRMT4, DNMT3B, and ASH2L, some of which are associated with differentiation decisions. Taken together, our results in NT2/D1 cells show that PRMT6 exerts predominantly H3R2me2a-independent functions in RNA splicing, which may contribute to pluripotency and neuronal identity.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123198","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}

引用次数: 0