Life Science Alliance最新文献_第3页

Structural roles of Ump1 and β-subunit propeptides in proteasome biogenesis. 蛋白酶体生物发生过程中 Ump1 和 β-亚基前肽的结构作用

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-09-11 DOI: 10.26508/lsa.202402865

Eric Mark,Paula C Ramos,Fleur Kayser,Jörg Höckendorff,R Jürgen Dohmen,Petra Wendler

引用次数: 0

Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b. 人类 mRNA 脱帽辅助因子同源物 DCP1a 和 DCP1b 的非冗余作用。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-09-10 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402938

Ivana Vukovic, Samantha M Barnada, Jonathan W Ruffin, Jon Karlin, Ravi Kumar Lokareddy, Gino Cingolani, Steven B McMahon

{"title":"Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b.","authors":"Ivana Vukovic, Samantha M Barnada, Jonathan W Ruffin, Jon Karlin, Ravi Kumar Lokareddy, Gino Cingolani, Steven B McMahon","doi":"10.26508/lsa.202402938","DOIUrl":"10.26508/lsa.202402938","url":null,"abstract":"Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2. As lower eukaryotes have a single DCP1 cofactor, the functional advantages gained by this evolutionary divergence remain unclear. We report the first functional dissection of DCP1a and DCP1b, demonstrating that they are non-redundant cofactors of DCP2 with unique roles in decapping complex integrity and specificity. DCP1a is essential for decapping complex assembly and interactions between the decapping complex and mRNA cap-binding proteins. DCP1b is essential for decapping complex interactions with protein degradation and translational machinery. DCP1a and DCP1b impact the turnover of distinct mRNAs. The observation that different ontological groups of mRNA molecules are regulated by DCP1a and DCP1b, along with their non-redundant roles in decapping complex integrity, provides the first evidence that these paralogs have qualitatively distinct functions.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290413","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

Mast cell extracellular trap formation underlies vascular and neural injury and hyperalgesia in sickle cell disease. 肥大细胞胞外陷阱的形成是镰状细胞病中血管和神经损伤以及痛觉减退的基础。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-09-06 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402788

Donovan A Argueta, Huy Tran, Yugal Goel, Aithanh Nguyen, Julia Nguyen, Stacy B Kiven, Chunsheng Chen, Fuad Abdulla, Gregory M Vercellotti, John D Belcher, Kalpna Gupta

{"title":"Mast cell extracellular trap formation underlies vascular and neural injury and hyperalgesia in sickle cell disease.","authors":"Donovan A Argueta, Huy Tran, Yugal Goel, Aithanh Nguyen, Julia Nguyen, Stacy B Kiven, Chunsheng Chen, Fuad Abdulla, Gregory M Vercellotti, John D Belcher, Kalpna Gupta","doi":"10.26508/lsa.202402788","DOIUrl":"10.26508/lsa.202402788","url":null,"abstract":"Sickle cell disease (SCD) is the most common inherited monogenetic disorder. Chronic and acute pain are hallmark features of SCD involving neural and vascular injury and inflammation. Mast cells reside in the vicinity of nerve fibers and vasculature, but how they influence these structures remains unknown. We therefore examined the mechanism of mast cell activation in a sickle microenvironment replete with cell-free heme and inflammation. Mast cells exposed to this environment showed an explosion of nuclear contents with the release of citrullinated histones, suggestive of mast cell extracellular trap (MCET) release. MCETs interacted directly with the vasculature and nerve fibers, a cause of vascular and neural injury in sickle cell mice. MCET formation was dependent upon peptidylarginine deiminase 4 (PAD4). Inhibition of PAD4 ameliorated vasoocclusion, chronic and acute hyperalgesia, and inflammation in sickle mice. PAD4 activation may also underlie neutrophil trap formation in SCD, thus providing a novel target to treat the sequelae of vascular and neural injury in SCD.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145939","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

Regulation of proteostasis by sleep through autophagy in Drosophila models of Alzheimer's disease. 在阿尔茨海默病果蝇模型中，睡眠通过自噬调节蛋白稳态。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-09-05 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402681

Natalie Ortiz-Vega, Amanda G Lobato, Tijana Canic, Yi Zhu, Stanislav Lazopulo, Sheyum Syed, R Grace Zhai

{"title":"Regulation of proteostasis by sleep through autophagy in Drosophila models of Alzheimer's disease.","authors":"Natalie Ortiz-Vega, Amanda G Lobato, Tijana Canic, Yi Zhu, Stanislav Lazopulo, Sheyum Syed, R Grace Zhai","doi":"10.26508/lsa.202402681","DOIUrl":"10.26508/lsa.202402681","url":null,"abstract":"Sleep and circadian rhythm dysfunctions are common clinical features of Alzheimer's disease (AD). Increasing evidence suggests that in addition to being a symptom, sleep disturbances can also drive the progression of neurodegeneration. Protein aggregation is a pathological hallmark of AD; however, the molecular pathways behind how sleep affects protein homeostasis remain elusive. Here we demonstrate that sleep modulation influences proteostasis and the progression of neurodegeneration in Drosophila models of tauopathy. We show that sleep deprivation enhanced Tau aggregational toxicity resulting in exacerbated synaptic degeneration. In contrast, sleep induction using gaboxadol led to reduced toxic Tau accumulation in neurons as a result of modulated autophagic flux and enhanced clearance of ubiquitinated Tau, suggesting altered protein processing and clearance that resulted in improved synaptic integrity and function. These findings highlight the complex relationship between sleep and regulation of protein homeostasis and the neuroprotective potential of sleep-enhancing therapeutics to slow the progression or delay the onset of neurodegeneration.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140487","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 novel role for CSA in the regulation of nuclear envelope integrity: uncovering a non-canonical function. CSA 在调节核包膜完整性中的新作用：发现一种非规范功能。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-29 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402745

Denny Yang, Austin Lai, Amelie Davies, Anne Fj Janssen, Matthew O Ellis, Delphine Larrieu

{"title":"A novel role for CSA in the regulation of nuclear envelope integrity: uncovering a non-canonical function.","authors":"Denny Yang, Austin Lai, Amelie Davies, Anne Fj Janssen, Matthew O Ellis, Delphine Larrieu","doi":"10.26508/lsa.202402745","DOIUrl":"10.26508/lsa.202402745","url":null,"abstract":"Cockayne syndrome (CS) is a premature ageing condition characterized by microcephaly, growth failure, and neurodegeneration. It is caused by mutations in ERCC6 or ERCC8 encoding for Cockayne syndrome B (CSB) and A (CSA) proteins, respectively. CSA and CSB have well-characterized roles in transcription-coupled nucleotide excision repair, responsible for removing bulky DNA lesions, including those caused by UV irradiation. Here, we report that CSA dysfunction causes defects in the nuclear envelope (NE) integrity. NE dysfunction is characteristic of progeroid disorders caused by a mutation in NE proteins, such as Hutchinson-Gilford progeria syndrome. However, it has never been reported in Cockayne syndrome. We observed CSA dysfunction affected LEMD2 incorporation at the NE and increased actin stress fibers that contributed to enhanced mechanical stress to the NE. Altogether, these led to NE abnormalities associated with the activation of the cGAS/STING pathway. Targeting the linker of the nucleoskeleton and cytoskeleton complex was sufficient to rescue these phenotypes. This work reveals NE dysfunction in a progeroid syndrome caused by mutations in a DNA damage repair protein, reinforcing the connection between NE deregulation and ageing.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116924","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

Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. 线粒体双链 RNA 的平衡取决于细胞周期的进展。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-29 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402764

Vanessa Xavier, Silvia Martinelli, Ryan Corbyn, Rachel Pennie, Kai Rakovic, Ian R Powley, Leah Officer-Jones, Vincenzo Ruscica, Alison Galloway, Leo M Carlin, Victoria H Cowling, John Le Quesne, Jean-Claude Martinou, Thomas MacVicar

{"title":"Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression.","authors":"Vanessa Xavier, Silvia Martinelli, Ryan Corbyn, Rachel Pennie, Kai Rakovic, Ian R Powley, Leah Officer-Jones, Vincenzo Ruscica, Alison Galloway, Leo M Carlin, Victoria H Cowling, John Le Quesne, Jean-Claude Martinou, Thomas MacVicar","doi":"10.26508/lsa.202402764","DOIUrl":"10.26508/lsa.202402764","url":null,"abstract":"Mitochondrial gene expression is a compartmentalised process essential for metabolic function. The replication and transcription of mitochondrial DNA (mtDNA) take place at nucleoids, whereas the subsequent processing and maturation of mitochondrial RNA (mtRNA) and mitoribosome assembly are localised to mitochondrial RNA granules. The bidirectional transcription of circular mtDNA can lead to the hybridisation of polycistronic transcripts and the formation of immunogenic mitochondrial double-stranded RNA (mt-dsRNA). However, the mechanisms that regulate mt-dsRNA localisation and homeostasis are largely unknown. With super-resolution microscopy, we show that mt-dsRNA overlaps with the RNA core and associated proteins of mitochondrial RNA granules but not nucleoids. Mt-dsRNA foci accumulate upon the stimulation of cell proliferation and their abundance depends on mitochondrial ribonucleotide supply by the nucleoside diphosphate kinase, NME6. Consequently, mt-dsRNA foci are profuse in cultured cancer cells and malignant cells of human tumour biopsies. Our results establish a new link between cell proliferation and mitochondrial nucleic acid homeostasis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108923","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

Differential modulation of polycomb-associated histone marks by cBAF, pBAF, and gBAF complexes. cBAF、pBAF 和 gBAF 复合物对多聚酶相关组蛋白标记的不同调节。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-29 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402715

Mary Bergwell, JinYoung Park, Jacob G Kirkland

{"title":"Differential modulation of polycomb-associated histone marks by cBAF, pBAF, and gBAF complexes.","authors":"Mary Bergwell, JinYoung Park, Jacob G Kirkland","doi":"10.26508/lsa.202402715","DOIUrl":"10.26508/lsa.202402715","url":null,"abstract":"Chromatin regulators alter the physical properties of chromatin to make it more or less permissive to transcription by modulating another protein's access to a specific DNA sequence through changes in nucleosome occupancy or histone modifications at a particular locus. Mammalian SWI/SNF complexes are a group of ATPase-dependent chromatin remodelers. In mouse embryonic stem cells, there are three primary forms of mSWI/SNF: canonical BAF (cBAF), polybromo-associated BAF (pBAF), and GLTSCR-associated BAF (gBAF). Nkx2-9 is bivalent, meaning nucleosomes at the locus have active and repressive modifications. In this study, we used unique BAF subunits to recruit each of the three complexes to Nkx2-9 using dCas9-mediated inducible recruitment (FIRE-Cas9). We show that recruitment of cBAF complexes leads to a significant loss of the polycomb repressive-2 H3K27me3 histone mark and polycomb repressive-1 and repressive-2 complex proteins, whereas gBAF and pBAF do not. Moreover, nucleosome occupancy alone cannot explain the loss of these marks. Our results demonstrate that cBAF has a unique role in the direct opposition of polycomb-associated histone modifications that gBAF and pBAF do not share.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108922","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

Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. 撤回：几丁质酶1通过TGFBRAP1和FOXO3调节TGF-β/SMAD7通路，从而调控肺纤维化

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-29 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402987

Chang-Min Lee, Chuan-Hua He, Jin Wook Park, Jae Hyun Lee, Suchitra Kamle, Bing Ma, Bedia Akosman, Roberto Cortez, Emily Chen, Yang Zhou, Erica L Herzog, Changwan Ryu, Xueyan Peng, Ivan O Rosas, Sergio Poli, Carol Feghali Bostwick, Augustine M Choi, Jack A Elias, Chun Geun Lee

引用次数: 0

Cryo-EM reveals a phosphorylated R-domain envelops the NBD1 catalytic domain in an ABC transporter. 冷冻电镜显示，磷酸化的 R-结构域包裹着 ABC 转运体中的 NBD1 催化结构域。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-29 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402779

Rodolpho Souza Amado de Carvalho, Md Shamiul Islam Rasel, Nitesh K Khandelwal, Thomas M Tomasiak

{"title":"Cryo-EM reveals a phosphorylated R-domain envelops the NBD1 catalytic domain in an ABC transporter.","authors":"Rodolpho Souza Amado de Carvalho, Md Shamiul Islam Rasel, Nitesh K Khandelwal, Thomas M Tomasiak","doi":"10.26508/lsa.202402779","DOIUrl":"10.26508/lsa.202402779","url":null,"abstract":"Many ATP-binding cassette transporters are regulated by phosphorylation on long and disordered loops which presents a challenge to visualize with structural methods. We have trapped an activated state of the regulatory domain (R-domain) of yeast cadmium factor 1 (Ycf1) by enzymatically enriching the phosphorylated state. A 3.23 Å cryo-EM structure reveals an R-domain structure with four phosphorylated residues and the position for the entire R-domain. The structure reveals key R-domain interactions including a bridging interaction between NBD1 and NBD2 and an interaction with the R-insertion, another regulatory region. We scanned these interactions by systematically replacing segments along the entire R-domain with scrambled combinations of alanine, glycine, and glutamine and probing function under cellular conditions that require the Ycf1 function. We find a close match with these interactions and interacting regions on our R-domain structure that points to the importance of most well-structured segments for function. We propose a model where the R-domain stabilizes a transport-competent state upon phosphorylation by enveloping NBD1 entirely.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108921","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

Helicobacter pylori induces the expression of Lgr5 and stem cell properties in gastric target cells. 幽门螺杆菌诱导胃靶细胞表达 Lgr5 和干细胞特性。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-08-27 Print Date: 2024-11-01 DOI: 10.26508/lsa.202402783

Zuzana Nascakova, Jiazhuo He, Giovanni Papa, Biel Francas, Flora Azizi, Anne Müller

{"title":"Helicobacter pylori induces the expression of Lgr5 and stem cell properties in gastric target cells.","authors":"Zuzana Nascakova, Jiazhuo He, Giovanni Papa, Biel Francas, Flora Azizi, Anne Müller","doi":"10.26508/lsa.202402783","DOIUrl":"10.26508/lsa.202402783","url":null,"abstract":"Helicobacter pylori infection predisposes carriers to a high risk of developing gastric cancer. The cell-of-origin of antral gastric cancer is the Lgr5+ stem cell. Here, we show that infection of antrum-derived gastric organoid cells with H. pylori increases the expression of the stem cell marker Lgr5 as determined by immunofluorescence microscopy, qRT-PCR, and Western blotting, both when cells are grown and infected as monolayers and when cells are exposed to H. pylori in 3D structures. H. pylori exposure increases stemness properties as determined by spheroid formation assay. Lgr5 expression and the acquisition of stemness depend on a functional type IV secretion system (T4SS) and at least partly on the T4SS effector CagA. The pharmacological inhibition or genetic ablation of NF-κB reverses the increase in Lgr5 and spheroid formation. Constitutively active Wnt/β-catenin signaling because of Apc inactivation exacerbates H. pylori-induced Lgr5 expression and stemness, both of which persist even after eradication of the infection. The combined data indicate that H. pylori has stemness-inducing properties that depend on its ability to activate NF-κB signaling.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080792","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