Molecular and Cellular Biology最新文献_第10页

Deubiquitinase OTUD1 Resolves Stalled Translation on polyA and Rare Codon Rich mRNAs. 去泛素酶OTUD1解决了多a和罕见的富含密码子的mrna上停滞的翻译。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-12-15 DOI: 10.1128/mcb.00265-22

Renata Snaurova, Alexander Vdovin, Michal Durech, Jakub Nezval, David Zihala, Tomas Jelinek, Roman Hajek, Michal Simicek

引用次数: 1

UBE3D Regulates mRNA 3'-End Processing and Maintains Adipogenic Potential in 3T3-L1 Cells. UBE3D调节3T3-L1细胞mRNA 3'-末端加工并维持脂肪生成潜能。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-12-15 DOI: 10.1128/mcb.00174-22

Daniel Heller-Trulli, Huiyun Liu, Srimoyee Mukherjee, Claire L Moore

{"title":"UBE3D Regulates mRNA 3'-End Processing and Maintains Adipogenic Potential in 3T3-L1 Cells.","authors":"Daniel Heller-Trulli, Huiyun Liu, Srimoyee Mukherjee, Claire L Moore","doi":"10.1128/mcb.00174-22","DOIUrl":"https://doi.org/10.1128/mcb.00174-22","url":null,"abstract":"We have previously described the role of an essential Saccharomyces cerevisiae gene, important for cleavage and polyadenylation 1 (IPA1), in the regulation of gene expression through its interaction with Ysh1, the endonuclease subunit of the mRNA 3′-end processing complex. Through a similar mechanism, the mammalian homolog ubiquitin protein ligase E3D (UBE3D) promotes the migratory and invasive potential of breast cancer cells, but its role in the regulation of gene expression during normal cellular differentiation has not previously been described. ABSTRACT We have previously described the role of an essential Saccharomyces cerevisiae gene, important for cleavage and polyadenylation 1 (IPA1), in the regulation of gene expression through its interaction with Ysh1, the endonuclease subunit of the mRNA 3′-end processing complex. Through a similar mechanism, the mammalian homolog ubiquitin protein ligase E3D (UBE3D) promotes the migratory and invasive potential of breast cancer cells, but its role in the regulation of gene expression during normal cellular differentiation has not previously been described. In this study, we show that CRISPR/Cas9-mediated knockout of Ube3d in 3T3-L1 cells blocks their ability to differentiate into mature adipocytes. Consistent with previous studies in other cell types, Ube3d knockout leads to decreased levels of CPSF73 and global changes in cellular mRNAs indicative of a loss of 3′-end processing capacity. Ube3d knockout cells also display decreased expression of known preadipogenic markers. Overexpression of either UBE3D or CPSF73 rescues the differentiation defect and partially restores protein levels of these markers. These results support a model in which UBE3D is necessary for the maintenance of the adipocyte-committed state via its regulation of the mRNA 3′-end processing machinery.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9753722/pdf/mcb.00174-22.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9633422","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

2022 Acknowledgment of Molecular and Cellular Biology Ad Hoc Reviewers. 2022分子和细胞生物学特设评审员鸣谢。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-12-01 DOI: 10.1128/mcb.00473-22

Peter Tontonoz

引用次数: 0

A Truncated Form of the p27 Cyclin-Dependent Kinase Inhibitor Translated from Pre-mRNA Causes G₂-Phase Arrest. 从Pre-mRNA翻译的p27周期蛋白依赖性激酶抑制剂的截断形式导致g2期阻滞。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-11-17 DOI: 10.1128/mcb.00217-22

Daisuke Kaida, Takayuki Satoh, Ken Ishida, Rei Yoshimoto, Kanae Komori

{"title":"A Truncated Form of the p27 Cyclin-Dependent Kinase Inhibitor Translated from Pre-mRNA Causes G2-Phase Arrest.","authors":"Daisuke Kaida, Takayuki Satoh, Ken Ishida, Rei Yoshimoto, Kanae Komori","doi":"10.1128/mcb.00217-22","DOIUrl":"https://doi.org/10.1128/mcb.00217-22","url":null,"abstract":"Pre-mRNA splicing is an indispensable mechanism for eukaryotic gene expression. Splicing inhibition causes cell cycle arrest at the G1 and G2/M phases, and this is thought to be one of the reasons for the potent antitumor activity of splicing inhibitors. However, the molecular mechanisms underlying the cell cycle arrest have many unknown aspects. In particular, the mechanism of G2/M-phase arrest caused by splicing inhibition is completely unknown. Here, we found that lower and higher concentrations of pladienolide B caused M-phase and G2-phase arrest, respectively. We analyzed protein levels of cell cycle regulators and found that a truncated form of the p27 cyclin-dependent kinase inhibitor, named p27*, accumulated in G2-arrested cells. Overexpression of p27* caused partial G2-phase arrest. Conversely, knockdown of p27* accelerated exit from G2/M phase after washout of splicing inhibitor. These results suggest that p27* contributes to G2/M-phase arrest caused by splicing inhibition. We also found that p27* bound to and inhibited M-phase cyclins, although it is well known that p27 regulates the G1/S transition. Intriguingly, p27*, but not full-length p27, was resistant to proteasomal degradation and remained in G2/M phase. These results suggest that p27*, which is a very stable truncated protein in G2/M phase, contributes to G2-phase arrest caused by splicing inhibition.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671031/pdf/mcb.00217-22.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9380740","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

Impact of Nuclear De Novo NAD⁺ Synthesis via Histone Dynamics on DNA Repair during Cellular Senescence To Prevent Tumorigenesis. 通过组蛋白动力学，细胞核新生NAD+合成对细胞衰老过程中DNA修复的影响，以防止肿瘤发生。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-11-17 DOI: 10.1128/mcb.00379-22

Masae Ikura, Kanji Furuya, Tomonari Matsuda, Tsuyoshi Ikura

{"title":"Impact of Nuclear De Novo NAD+ Synthesis via Histone Dynamics on DNA Repair during Cellular Senescence To Prevent Tumorigenesis.","authors":"Masae Ikura, Kanji Furuya, Tomonari Matsuda, Tsuyoshi Ikura","doi":"10.1128/mcb.00379-22","DOIUrl":"https://doi.org/10.1128/mcb.00379-22","url":null,"abstract":"NAD+ synthesis is a fundamental process in living cells. The effects of local metabolite production on chromatin influence the epigenetic status of chromatin in DNA metabolism. We have previously shown that K5 acetylation of H2AX by TIP60 is required for the ADP ribosylation activity of PARP-1, for histone H2AX exchange at DNA damage sites. However, the detailed molecular mechanism has remained unclear. Here, we identified de novo NAD synthetase 1 (NAD syn1) as a novel binding partner to H2AX. The enzymatic activity of NAD syn1 is crucial for the ADP ribosylation activity of PARP-1 for the H2AX dynamics at sites of DNA damage. Inhibition of the NAD synthetase activity in the cell nucleus decreased the overall cellular NAD+ concentration, leading to cellular senescence. Accordingly, the acetylation-dependent H2AX dynamics and homologous recombination repair were suppressed, leading to increased tumorigenesis. Our findings have revealed the importance of de novo NAD+ production in the cell nucleus for protection against the decreased DNA repair capacity caused by cellular senescence and thus against tumorigenesis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670974/pdf/mcb.00379-22.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710728","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: 1

Nuanced Interactions between AKAP79 and STIM1 with Orai1 Ca²⁺ Channels at Endoplasmic Reticulum-Plasma Membrane Junctions Sustain NFAT Activation. 在内质网-质膜连接处AKAP79和STIM1与Orai1 Ca2+通道之间的微妙相互作用维持NFAT激活。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-11-17 DOI: 10.1128/mcb.00175-22

Yu-Ping Lin, Erica Scappini, Carlos Landaverde, Frederick Parekh-Glitsch, Charles J Tucker, Gary R Mirams, Anant B Parekh

{"title":"Nuanced Interactions between AKAP79 and STIM1 with Orai1 Ca2+ Channels at Endoplasmic Reticulum-Plasma Membrane Junctions Sustain NFAT Activation.","authors":"Yu-Ping Lin, Erica Scappini, Carlos Landaverde, Frederick Parekh-Glitsch, Charles J Tucker, Gary R Mirams, Anant B Parekh","doi":"10.1128/mcb.00175-22","DOIUrl":"https://doi.org/10.1128/mcb.00175-22","url":null,"abstract":"A-kinase anchoring protein 79 (AKAP79) is a human scaffolding protein that organizes Ca2+/calmodulin-dependent protein phosphatase calcineurin, calmodulin, cAMP-dependent protein kinase, protein kinase C, and the transcription factor nuclear factor of activated T cells (NFAT1) into a signalosome at the plasma membrane. Upon Ca2+ store depletion, AKAP79 interacts with the N-terminus of STIM1-gated Orai1 Ca2+ channels, enabling Ca2+ nanodomains to stimulate calcineurin. Calcineurin then dephosphorylates and activates NFAT1, which then translocates to the nucleus. A fundamental question is how signalosomes maintain long-term signaling when key effectors are released and therefore removed beyond the reach of the activating signal. Here, we show that the AKAP79-Orai1 interaction is considerably more transient than that of STIM1-Orai1. Free AKAP79, with calcineurin and NFAT1 in tow, is able to replace rapidly AKAP79 devoid of NFAT1 on Orai1, in the presence of continuous Ca2+ entry. We also show that Ca2+ nanodomains near Orai1 channels activate almost the entire cytosolic pool of NFAT1. Recycling of inactive NFAT1 from the cytoplasm to AKAP79 in the plasma membrane, coupled with the relatively weak interaction between AKAP79 and Orai1, maintain excitation-transcription coupling. By measuring rates for AKAP79-NFAT interaction, we formulate a mathematical model that simulates NFAT dynamics at the plasma membrane.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670898/pdf/mcb.00175-22.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9373933","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: 1

Identification of PAX6 and NFAT4 as the Transcriptional Regulators of the Long Noncoding RNA Mrhl in Neuronal Progenitors. PAX6和NFAT4作为神经元祖细胞长链非编码RNA Mrhl转录调控因子的鉴定

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-11-17 DOI: 10.1128/mcb.00036-22

Debosree Pal, Sangeeta Dutta, Dhanur P Iyer, Deepika Shriram, Utsa Bhaduri, M R S Rao

{"title":"Identification of PAX6 and NFAT4 as the Transcriptional Regulators of the Long Noncoding RNA Mrhl in Neuronal Progenitors.","authors":"Debosree Pal, Sangeeta Dutta, Dhanur P Iyer, Deepika Shriram, Utsa Bhaduri, M R S Rao","doi":"10.1128/mcb.00036-22","DOIUrl":"https://doi.org/10.1128/mcb.00036-22","url":null,"abstract":"The long noncoding RNA (lncRNA) Mrhl has been shown to be involved in coordinating meiotic commitment of mouse spermatogonial progenitors and differentiation events in mouse embryonic stem cells. Here, we characterized the interplay of Mrhl with lineage-specific transcription factors during mouse neuronal lineage development. Our results demonstrate that Mrhl is expressed in the neuronal progenitor populations in mouse embryonic brains and in retinoic acid-derived radial-glia-like neuronal progenitor cells. Depletion of Mrhl leads to early differentiation of neuronal progenitors to a more committed state. A master transcription factor, PAX6, directly binds to the Mrhl promoter at a major site in the distal promoter, located at 2.9 kb upstream of the transcription start site (TSS) of Mrhl. Furthermore, NFAT4 occupies the Mrhl-proximal promoter at two sites, at 437 base pairs (bp) and 143 bp upstream of the TSS. Independent knockdown studies for PAX6 and NFAT4 confirm that they regulate Mrhl expression in neuronal progenitors. We also show that PAX6 and NFAT4 associate with each other in the same chromatin complex. NFAT4 occupies the Mrhl promoter in PAX6-bound chromatin, implying possible coregulation of Mrhl. Our studies are crucial for understanding how lncRNAs are regulated by major lineage-specific transcription factors, in order to define specific development and differentiation events.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670966/pdf/mcb.00036-22.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9380745","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: 1

Biochemical Characterization of the TINTIN Module of the NuA4 Complex Reveals Allosteric Regulation of Nucleosome Interaction. NuA4复合物TINTIN模块的生化表征揭示了核小体相互作用的变构调节。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-11-17 DOI: 10.1128/mcb.00170-22

Udit Dalwadi, Elaina Corrado, Kaelin D Fleming, Brandon E Moeller, Sung-Eun Nam, John E Burke, Calvin K Yip

{"title":"Biochemical Characterization of the TINTIN Module of the NuA4 Complex Reveals Allosteric Regulation of Nucleosome Interaction.","authors":"Udit Dalwadi, Elaina Corrado, Kaelin D Fleming, Brandon E Moeller, Sung-Eun Nam, John E Burke, Calvin K Yip","doi":"10.1128/mcb.00170-22","DOIUrl":"https://doi.org/10.1128/mcb.00170-22","url":null,"abstract":"Trimer Independent of NuA4 involved in Transcription Interactions with Nucleosomes (TINTIN) is an integral module of the essential yeast lysine acetyltransferase complex NuA4 that plays key roles in transcription regulation and DNA repair. Composed of Eaf3, Eaf5, and Eaf7, TINTIN mediates targeting of NuA4 to chromatin through the chromodomain-containing subunit Eaf3 that is shared with the Rpd3S histone deacetylase complex. How Eaf3 mediates chromatin interaction in the context of TINTIN and how is it different from what has been observed in Rpd3S is unclear. Here, we reconstituted recombinant TINTIN and its subassemblies and characterized their biochemical and structural properties. Our coimmunoprecipitation, AlphaFold2 modeling, and hydrogen deuterium exchange mass spectrometry (HDX-MS) analyses revealed that the Eaf3 MRG domain contacts Eaf7 and this binding induces conformational changes throughout Eaf3. Nucleosome-binding assays showed that Eaf3 and TINTIN interact non-specifically with the DNA on nucleosomes. Furthermore, integration into TINTIN enhances the affinity of Eaf3 toward nucleosomes and this improvement is a result of allosteric activation of the Eaf3 chromodomain. Negative stain electron microscopy (EM) analysis revealed that TINTIN binds to the edge of nucleosomes with increased specificity in the presence of H3K36me3. Collectively, our work provides insights into the dynamics of TINTIN and the mechanism by which its interactions with chromatin are regulated.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670870/pdf/mcb.00170-22.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9605409","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: 2

Arginylation Regulates Cytoskeleton Organization and Cell Division and Affects Mitochondria in Fission Yeast. 精氨酸化对分裂酵母细胞骨架组织和细胞分裂的调控及对线粒体的影响。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-11-17 DOI: 10.1128/mcb.00261-22

Li Chen, Anna Kashina

{"title":"Arginylation Regulates Cytoskeleton Organization and Cell Division and Affects Mitochondria in Fission Yeast.","authors":"Li Chen, Anna Kashina","doi":"10.1128/mcb.00261-22","DOIUrl":"https://doi.org/10.1128/mcb.00261-22","url":null,"abstract":"Protein arginylation mediated by arginyltransferase Ate1 is a posttranslational modification of emerging importance implicated in the regulation of mammalian embryogenesis, the cardiovascular system, tissue morphogenesis, cell migration, neurodegeneration, cancer, and aging. Ate1 deletion results in embryonic lethality in mice but does not affect yeast viability, making yeast an ideal system to study the molecular pathways regulated by arginylation. Here, we conducted a global analysis of cytoskeleton-related arginylation-dependent phenotypes in Schizosaccharomyces pombe, a fission yeast species that shares many fundamental features of higher eukaryotic cells. Our studies revealed roles of Ate1 in cell division, cell polarization, organelle transport, and interphase cytoskeleton organization and dynamics. We also found a role of Ate1 in mitochondria morphology and maintenance. Furthermore, targeted mass spectrometry analysis of the total Sc. pombe arginylome identified a number of arginylated proteins, including those that play direct roles in these processes; lack of their arginylation may be responsible for ate1-knockout phenotypes. Our work outlines global biological processes potentially regulated by arginylation and paves the way to unraveling the functions of protein arginylation that are conserved at multiple levels of evolution and potentially constitute the primary role of this modification in vivo.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670973/pdf/mcb.00261-22.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9290056","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: 1

Correction for Malik et al., "Structural and Functional Organization of TRAP220, the TRAP/Mediator Subunit That Is Targeted by Nuclear Receptors". 修正Malik等人的“TRAP220的结构和功能组织，TRAP220是核受体靶向的TRAP/中介亚基”。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2022-11-17 Epub Date: 2022-10-18 DOI: 10.1128/mcb.00359-22

Sohail Malik, Mohamed Guermah, Chao-Xing Yuan, Weizhen Wu, Soichiro Yamamura, Robert G Roeder

引用次数: 6