FEBS Letters最新文献

{"title":"Molecular dissection of ALS-linked TDP-43 - involvement of the Gly-rich domain in interaction with G-quadruplex mRNA.","authors":"Akira Ishiguro,&nbsp;Nobuyuki Kimura,&nbsp;Takashi Noma,&nbsp;Rieko Shimo-Kon,&nbsp;Akira Ishihama,&nbsp;Takahide Kon","doi":"10.1002/1873-3468.13800","DOIUrl":"https://doi.org/10.1002/1873-3468.13800","url":null,"abstract":"<p><p>TDP-43 is the major pathogenic protein of amyotrophic lateral sclerosis (ALS). Previously, we identified that TDP-43 interacts with G-quadruplex (G4)-containing RNA and is involved in their long-distance transport in neurons. For the molecular dissection of the TDP-43 and G4-RNA interaction, we analyzed it here in vitro and in cultured cells using a set of 10 mutant TDP-43 proteins from familial and sporadic ALS patients as well as using the TDP-43 C-terminal Gly-rich domain alone. Our results altogether indicate the involvement of the Gly-rich region of TDP-43 in the initial recognition and binding of G4-RNA, which then induces tight binding of TDP-43 with target RNAs, supposedly in conjunction with its RNA recognition motifs.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"594 14","pages":"2254-2265"},"PeriodicalIF":3.5,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37874930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial","authors":"A. Barr","doi":"10.1002/1873-3468.13869","DOIUrl":"https://doi.org/10.1002/1873-3468.13869","url":null,"abstract":"We are delighted to publish Part 2 of our Special Issue on cell cycle control. Here, we present four reviews that, together with Part 1, give a comprehensive overview of our current understanding of the cell cycle, as well as the methods employed to study it, the roles of cell cycle proteins beyond orchestrating cell division, and some of the key outstanding questions. Part 1 provided an overview of the common principles governing the transitions between the cell cycle phases [1], the role of metabolism in quiescence–proliferation transitions [2] and the relationship between the speed of the cell cycle and cell fate [3]. In addition, Part 1 covered how cells prepare for DNA replication during G1 and how this impacts proper DNA replication in S-phase [4], how cells control entry into mitosis [5] and, once in mitosis, how they achieve proper chromosome alignment and equal segregation of chromosomes into two daughter cells [6], and how mitotic exit is controlled to ensure appropriate temporal and spatial organisation [7]. A comparison between the function of CDKs in mitosis and meiosis concluded Part 1 [8]. Part 2 begins with a review from Silvia Santos’ Lab that covers how embryonic cell cycles remodel in order to give rise to somatic cell cycles, including the, often forgotten, differences between human and mouse embryonic stem cells [9]. Adaptation of embryonic cell cycles to somatic cell cycles requires extensive changes in the regulation of cyclins, CDKs and the anaphasepromoting complex/cyclosome, as well as the introduction of cell cycle checkpoints. A notable example of the checkpoints that are introduced en route to somatic cell cycles is the restriction point. The restriction point is defined as the point in the cell cycle beyond which cells no longer require input from mitogens to complete cell division. In a review from our laboratory, we discuss and analyse recent data to understand the control of the restriction point in determining proliferation–quiescence decisions in cells [10]. The restriction point was originally defined over 40 years ago, yet its position within the cell cycle and the molecular basis for this decision are still active topics of investigation. From proliferation–quiescence decisions, we then move onto proliferation–differentiation decisions, in a review from the Kimata and Aradhya laboratories [11]. Much has been written in this review series about the roles of cyclin:CDK complexes in driving the cell cycle. However, here the focus is on the cell cycle-independent roles of cyclins, CDKs and their inhibitors, in particular in their contributions to cell differentiation. It is critical to remember these non-cell cycle functions, particularly when analysing the phenotypes of mice where the function of these proteins has been disrupted. Finally, Anna Eastman and Shangqin Guo have provided a second review for this series, and this one focussed on the methods available to study and probe the cell cycle [12]. We imagine ","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42462181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholino-ncRNAs modulate sex-specific- and age-related acetylcholine signals.","authors":"Nimrod Madrer,&nbsp;Hermona Soreq","doi":"10.1002/1873-3468.13789","DOIUrl":"https://doi.org/10.1002/1873-3468.13789","url":null,"abstract":"<p><p>Acetylcholine (ACh) signaling orchestrates mammalian movement, mental capacities, and inflammation. Dysregulated ACh signaling associates with many human mental disorders and neurodegeneration in an individual-, sex-, and tissue-related manner. Moreover, aged patients under anticholinergic therapy show increased risk of dementia, but the underlying molecular mechanisms are incompletely understood. Here, we report that certain cholinergic-targeting noncoding RNAs, named Cholino-noncoding RNAs (ncRNAs), can modulate ACh signaling, agonistically or antagonistically, via distinct direct and indirect mechanisms and at different timescales. Cholino-ncRNAs include both small microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). The former may attenuate translation and/or induce destruction of target mRNAs that code for either ACh-signaling proteins or transcription factors controlling the expression of cholinergic genes. lncRNAs may block miRNAs via 'sponging' events or by competitive binding to the cholinergic target mRNAs. Also, single nucleotide polymorphisms in either Cholino-ncRNAs or in their recognition sites in the ACh-signaling associated genes may modify ACh signaling-regulated processes. Taken together, both inherited and acquired changes in the function of Cholino-ncRNAs impact ACh-related deficiencies, opening new venues for individual, sex-related, and age-specific oriented research, diagnosis, and therapeutics.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"594 14","pages":"2185-2198"},"PeriodicalIF":3.5,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37868644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restriction point regulation at the crossroads between quiescence and cell proliferation.","authors":"Betheney R Pennycook, Alexis R Barr","doi":"10.1002/1873-3468.13867","DOIUrl":"10.1002/1873-3468.13867","url":null,"abstract":"<p><p>The coordination of cell proliferation with reversible cell cycle exit into quiescence is crucial for the development of multicellular organisms and for tissue homeostasis in the adult. The decision between quiescence and proliferation occurs at the restriction point, which is widely thought to be located in the G1 phase of the cell cycle, when cells integrate accumulated extracellular and intracellular signals to drive this binary cellular decision. On the molecular level, decision-making is exerted through the activation of cyclin-dependent kinases (CDKs). CDKs phosphorylate the retinoblastoma (Rb) transcriptional repressor to regulate the expression of cell cycle genes. Recently, the classical view of restriction point regulation has been challenged. Here, we review the latest findings on the activation of CDKs, Rb phosphorylation and the nature and position of the restriction point within the cell cycle.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2020-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38071901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From clocks to dominoes: lessons on cell cycle remodelling from embryonic stem cells.","authors":"Joe Padgett, Silvia D M Santos","doi":"10.1002/1873-3468.13862","DOIUrl":"10.1002/1873-3468.13862","url":null,"abstract":"<p><p>Cell division is a fundamental cellular process and the evolutionarily conserved networks that control cell division cycles adapt during development, tissue regeneration, cell de-differentiation and reprogramming, and a variety of pathological conditions. Embryonic development is a prime example of such versatility: fast, clock-like divisions hallmarking embryonic cells at early developmental stages become slower and controlled during cellular differentiation and lineage specification. In this review, we compare and contrast the unique cell cycle of mouse and human embryonic stem cells with that of early embryonic cells and of differentiated cells. We propose that embryonic stem cells provide an extraordinarily useful model system to understand cell cycle remodelling during embryonic-to-somatic transitions. We discuss how cell cycle networks help sustain embryonic stem cell pluripotency and self-renewal and how they safeguard cell identity and proper cell number in differentiated cells. Finally, we highlight the incredible diversity in cell cycle regulation within mammals and discuss the implications of studying cell cycle remodelling for understanding healthy and disease states.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2020-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38046233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 spike glycoprotein-binding proteins expressed by upper respiratory tract bacteria may prevent severe viral infection.","authors":"Kourosh Honarmand Ebrahimi","doi":"10.1002/1873-3468.13845","DOIUrl":"10.1002/1873-3468.13845","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global challenge. The virus infects host cells using its spike glycoprotein (S-protein) and has significantly higher infectivity and mortality rates among the aged population. Here, based on bioinformatic analysis, I provide evidence that some members of the upper respiratory tract (URT) commensal bacteria express viral S-protein -binding proteins. Based on this analysis and available data showing a decline in the population of these bacteria in the elderly, I propose that some URT commensal bacteria hamper SARS-CoV-2 infectivity and that a decline in the population of these bacteria contributes to the severity of infection. Further studies should provide a better understanding of the interaction of URT bacteria and SARS-CoV-2, which may lead to new therapeutic approaches.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"594 11","pages":"1651-1660"},"PeriodicalIF":3.5,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280584/pdf/FEB2-594-1651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37970743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The palette of techniques for cell cycle analysis.","authors":"Anna E Eastman, Shangqin Guo","doi":"10.1002/1873-3468.13842","DOIUrl":"10.1002/1873-3468.13842","url":null,"abstract":"<p><p>The cell division cycle is the generational period of cellular growth and propagation. Cell cycle progression needs to be highly regulated to preserve genomic fidelity while increasing cell number. In multicellular organisms, the cell cycle must also coordinate with cell fate specification during development and tissue homeostasis. Altered cell cycle dynamics play a central role also in a number of pathophysiological processes. Thus, extensive effort has been made to define the biochemical machineries that execute the cell cycle and their regulation, as well as implementing more sensitive and accurate cell cycle measurements. Here, we review the available techniques for cell cycle analysis, revisiting the assumptions behind conventional population-based measurements and discussing new tools to better address cell cycle heterogeneity in the single-cell era. We weigh the strengths, weaknesses, and trade-offs of methods designed to measure temporal aspects of the cell cycle. Finally, we discuss emerging techniques for capturing cell cycle speed at single-cell resolution in live animals.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2020-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261528/pdf/nihms-1817637.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37965800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of metazoan cell cycle regulators as coordinators of the cell cycle and differentiation.","authors":"Yuu Kimata, Maïté Leturcq, Rajaguru Aradhya","doi":"10.1002/1873-3468.13805","DOIUrl":"10.1002/1873-3468.13805","url":null,"abstract":"<p><p>In multicellular organisms, cell proliferation must be tightly coordinated with other developmental processes to form functional tissues and organs. Despite significant advances in our understanding of how the cell cycle is controlled by conserved cell-cycle regulators (CCRs), how the cell cycle is coordinated with cell differentiation in metazoan organisms and how CCRs contribute to this process remain poorly understood. Here, we review the emerging roles of metazoan CCRs as intracellular proliferation-differentiation coordinators in multicellular organisms. We illustrate how major CCRs regulate cellular events that are required for cell fate acquisition and subsequent differentiation. To this end, CCRs employ diverse mechanisms, some of which are separable from those underpinning the conventional cell-cycle-regulatory functions of CCRs. By controlling cell-type-specific specification/differentiation processes alongside the progression of the cell cycle, CCRs enable spatiotemporal coupling between differentiation and cell proliferation in various developmental contexts in vivo. We discuss the significance and implications of this underappreciated role of metazoan CCRs for development, disease and evolution.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2020-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37913447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cascading proton transfers are a hallmark of the catalytic mechanism of SAM-dependent methyltransferases.","authors":"Li Na Zhao, Philipp Kaldis","doi":"10.1002/1873-3468.13799","DOIUrl":"10.1002/1873-3468.13799","url":null,"abstract":"<p><p>The S-adenosyl methionine (SAM)-dependent methyltransferases attach a methyl group to the deprotonated methyl lysine using SAM as a donor. An intriguing, yet unanswered, question is how the deprotonation takes place. PRDM9 with well-defined enzyme activity is a good representative of the methyltransferase family to study the deprotonation and subsequently the methyl transfer. Our study has found that the pKa of Tyr357 is low enough to make it an ideal candidate for proton abstraction from the methyl lysine. The partially deprontonated Tyr357 is able to change its H-bond pattern thus bridging two proton tunneling states and providing a cascading proton transfer. We have uncovered a new catalytic mechanism for the deprotonation of the methyl lysine in methyltransferases.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2020-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37888026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand‐dependent intra‐ and interdomain motions in the PDZ12 tandem regulate binding interfaces in postsynaptic density protein‐95","authors":"Bertalan Kovács, Nóra Zajácz-Epresi, Zoltán Gáspári","doi":"10.1002/1873-3468.13626","DOIUrl":"https://doi.org/10.1002/1873-3468.13626","url":null,"abstract":"The postsynaptic density protein‐95 (PSD‐95) regulates synaptic plasticity through interactions mediated by its peptide‐binding PDZ domains. The two N‐terminal PDZ domains of PSD‐95 form an autonomous structural unit, and their interdomain orientation and dynamics depend on ligand binding. To understand the mechanistic details of the effect of ligand binding, we generated conformational ensembles using available experimentally determined nuclear Overhauser effect interatomic distances and S2 order parameters. In our approach, the fast dynamics of the two domains is treated independently. We find that intradomain structural changes induced by ligand binding modulate the probability of the occurrence of specific domain–domain orientations. Our results suggest that the β2‐β3 loop in the PDZ domains is a key regulatory region, which influences both intradomain motions and supramodular rearrangement.","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45330385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}