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  • Molecular analysis and essentiality of Aro1 shikimate biosynthesis
           multi-enzyme in Candida albicans

    • Authors: Stogios, P. J; Liston, S. D, Semper, C, Quade, B, Michalska, K, Evdokimova, E, Ram, S, Otwinowski, Z, Borek, D, Cowen, L. E, Savchenko, A.
      Abstract: In the human fungal pathogen Candida albicans, ARO1 encodes an essential multi-enzyme that catalyses consecutive steps in the shikimate pathway for biosynthesis of chorismate, a precursor to folate and the aromatic amino acids. We obtained the first molecular image of C. albicans Aro1 that reveals the architecture of all five enzymatic domains and their arrangement in the context of the full-length protein. Aro1 forms a flexible dimer allowing relative autonomy of enzymatic function of the individual domains. Our activity and in cellulo data suggest that only four of Aro1’s enzymatic domains are functional and essential for viability of C. albicans, whereas the 3-dehydroquinate dehydratase (DHQase) domain is inactive because of active site substitutions. We further demonstrate that in C. albicans, the type II DHQase Dqd1 can compensate for the inactive DHQase domain of Aro1, suggesting an unrecognized essential role for this enzyme in shikimate biosynthesis. In contrast, in Candida glabrata and Candida parapsilosis, which do not encode a Dqd1 homolog, Aro1 DHQase domains are enzymatically active, highlighting diversity across Candida species.
      Keywords: Structural Biology
      PubDate: 2022-05-05T08:18:03-07:00
      DOI: 10.26508/lsa.202101358
      Issue No: Vol. 5, No. 8 (2022)
       
  • Molecular insights into RNA recognition and gene regulation by the
           TRIM-NHL protein Mei-P26

    • Authors: Salerno-Kochan, A; Horn, A, Ghosh, P, Nithin, C, Koscielniak, A, Meindl, A, Strauss, D, Krutyhołowa, R, Rossbach, O, Bujnicki, J. M, Gaik, M, Medenbach, J, Glatt, S.
      Abstract: The TRIM-NHL protein Meiotic P26 (Mei-P26) acts as a regulator of cell fate in Drosophila. Its activity is critical for ovarian germline stem cell maintenance, differentiation of oocytes, and spermatogenesis. Mei-P26 functions as a post-transcriptional regulator of gene expression; however, the molecular details of how its NHL domain selectively recognizes and regulates its mRNA targets have remained elusive. Here, we present the crystal structure of the Mei-P26 NHL domain at 1.6 Å resolution and identify key amino acids that confer substrate specificity and distinguish Mei-P26 from closely related TRIM-NHL proteins. Furthermore, we identify mRNA targets of Mei-P26 in cultured Drosophila cells and show that Mei-P26 can act as either a repressor or activator of gene expression on different RNA targets. Our work reveals the molecular basis of RNA recognition by Mei-P26 and the fundamental functional differences between otherwise very similar TRIM-NHL proteins.
      Keywords: Molecular Biology, Stem Cells, Structural Biology
      PubDate: 2022-05-05T08:18:03-07:00
      DOI: 10.26508/lsa.202201418
      Issue No: Vol. 5, No. 8 (2022)
       
  • Analyzing efficacy, stability, and safety of AAV-mediated optogenetic
           hearing restoration in mice

    • Authors: Bali, B; Gruber-Dujardin, E, Kusch, K, Rankovic, V, Moser, T.
      Abstract: AAV-mediated optogenetic neural stimulation has become a clinical approach for restoring function in sensory disorders and feasibility for hearing restoration has been indicated in rodents. Nonetheless, long-term stability and safety of AAV-mediated channelrhodopsin (ChR) expression in spiral ganglion neurons (SGNs) remained to be addressed. Here, we used longitudinal studies on mice subjected to early postnatal administration of AAV2/6 carrying fast gating ChR f-Chrimson under the control of the human synapsin promoter unilaterally to the cochlea. f-Chrimson expression in SGNs in both ears and the brain was probed in animals aged 1 mo to 2 yr. f-Chrimson was observed in SGNs at all ages indicating longevity of ChR-expression. SGN numbers in the AAV-injected cochleae declined with age faster than in controls. Investigations were extended to the brain in which viral transduction was observed across the organ at varying degrees irrespective of age without observing viral spread-related pathologies. No viral DNA or virus-related histopathological findings in visceral organs were encountered. In summary, our study demonstrates life-long (24 mo in mice) expression of f-Chrimson in SGNs upon single AAV-dosing of the cochlea.
      Keywords: Genetics, Gene Therapy & Genetic Disease, Neuroscience
      PubDate: 2022-05-05T07:57:13-07:00
      DOI: 10.26508/lsa.202101338
      Issue No: Vol. 5, No. 8 (2022)
       
  • Systematic identification of ALK substrates by integrated phosphoproteome
           and interactome analysis

    • Authors: Adachi, J; Kakudo, A, Takada, Y, Isoyama, J, Ikemoto, N, Abe, Y, Narumi, R, Muraoka, S, Gunji, D, Hara, Y, Katayama, R, Tomonaga, T.
      Abstract: The sensitivity of phosphorylation site identification by mass spectrometry has improved markedly. However, the lack of kinase–substrate relationship (KSR) data hinders the improvement of the range and accuracy of kinase activity prediction. In this study, we aimed to develop a method for acquiring systematic KSR data on anaplastic lymphoma kinase (ALK) using mass spectrometry and to apply this method to the prediction of kinase activity. Thirty-seven ALK substrate candidates, including 34 phosphorylation sites not annotated in the PhosphoSitePlus database, were identified by integrated analysis of the phosphoproteome and crosslinking interactome of HEK 293 cells with doxycycline-induced ALK overexpression. Furthermore, KSRs of ALK were validated by an in vitro kinase assay. Finally, using phosphoproteomic data from ALK mutant cell lines and patient-derived cells treated with ALK inhibitors, we found that the prediction of ALK activity was improved when the KSRs identified in this study were used instead of the public KSR dataset. Our approach is applicable to other kinases, and future identification of KSRs will facilitate more accurate estimations of kinase activity and elucidation of phosphorylation signals.
      Keywords: Cancer, Cell Biology
      PubDate: 2022-05-04T11:13:06-07:00
      DOI: 10.26508/lsa.202101202
      Issue No: Vol. 5, No. 8 (2022)
       
  • Reduced adhesion of aged intestinal stem cells contributes to an
           accelerated clonal drift

    • Authors: Hageb, A; Thalheim, T, Nattamai, K. J, Möhrle, B, Sacma, M, Sakk, V, Thielecke, L, Cornils, K, Grandy, C, Port, F, Gottschalk, K.-E, Mallm, J.-P, Glauche, I, Galle, J, Mulaw, M. A, Geiger, H.
      Abstract: Upon aging, the function of the intestinal epithelium declines with a concomitant increase in aging-related diseases. ISCs play an important role in this process. It is known that ISC clonal dynamics follow a neutral drift model. However, it is not clear whether the drift model is still valid in aged ISCs. Tracking of clonal dynamics by clonal tracing revealed that aged crypts drift into monoclonality substantially faster than young ones. However, ISC tracing experiments, in vivo and ex vivo, implied a similar clonal expansion ability of both young and aged ISCs. Single-cell RNA sequencing for 1,920 high Lgr5 ISCs from young and aged mice revealed increased heterogeneity among subgroups of aged ISCs. Genes associated with cell adhesion were down-regulated in aged ISCs. ISCs of aged mice indeed show weaker adhesion to the matrix. Simulations applying a single cell–based model of the small intestinal crypt demonstrated an accelerated clonal drift at reduced adhesion strength, implying a central role for reduced adhesion for affecting clonal dynamics upon aging.
      Keywords: Aging, Stem Cells, Systems & Computational Biology
      PubDate: 2022-04-29T10:32:15-07:00
      DOI: 10.26508/lsa.202201408
      Issue No: Vol. 5, No. 8 (2022)
       
  • Subgenomic RNA profiling suggests novel mechanism in coronavirus gene
           regulation and host adaption

    • Authors: Lyu, L; Feng, R, Zhang, M, Xie, X, Liao, Y, Zhou, Y, Guo, X, Su, B, Dorsett, Y, Chen, L.
      Abstract: Fundamental to viral biology is identification and annotation of viral genes and their function. Determining the level of coronavirus gene expression is inherently difficult due to the positive stranded RNA genome and the identification of subgenomic RNAs (sgRNAs) that are required for expression of most viral genes. We developed a bioinformatic pipeline to analyze metatranscriptomic data from 20 independent studies encompassing 588 individual samples and 10 coronavirus species. This comparative analysis defined a core sgRNA repertoire for SARS-CoV-2 and found novel sgRNAs that could encode functional short peptides. Relevant to coronavirus infectivity and transmission, we also observed that the ratio of Spike sgRNA to Nucleocapsid one is highest in SARS-CoV-2, among the β-coronaviruses examined. Furthermore, the adjustment of this ratio can be made by modifications to the viral RNA replication machinery, representing a form of viral gene regulation that may be involved in host adaption.
      Keywords: Methods & Resources, Microbiology, Virology & Host Pathogen Interaction, Systems & Computational Biology
      PubDate: 2022-04-25T06:15:38-07:00
      DOI: 10.26508/lsa.202101347
      Issue No: Vol. 5, No. 8 (2022)
       
  • Nutrient sensitive protein O-GlcNAcylation modulates the transcriptome
           through epigenetic mechanisms during embryonic neurogenesis

    • Authors: Parween, S; Alawathugoda, T. T, Prabakaran, A. D, Dheen, S. T, Morse, R. H, Emerald, B. S, Ansari, S. A.
      Abstract: Protein O-GlcNAcylation is a dynamic, nutrient-sensitive mono-glycosylation deposited on numerous nucleo-cytoplasmic and mitochondrial proteins, including transcription factors, epigenetic regulators, and histones. However, the role of protein O-GlcNAcylation on epigenome regulation in response to nutrient perturbations during development is not well understood. Herein we recapitulated early human embryonic neurogenesis in cell culture and found that pharmacological up-regulation of O-GlcNAc levels during human embryonic stem cells’ neuronal differentiation leads to up-regulation of key neurogenic transcription factor genes. This transcriptional de-repression is associated with reduced H3K27me3 and increased H3K4me3 levels on the promoters of these genes, perturbing promoter bivalency possibly through increased EZH2-Thr311 phosphorylation. Elevated O-GlcNAc levels also lead to increased Pol II-Ser5 phosphorylation and affect H2BS112O-GlcNAc and H2BK120Ub1 on promoters. Using an in vivo rat model of maternal hyperglycemia, we show similarly elevated O-GlcNAc levels and epigenetic dysregulations in the developing embryo brains because of hyperglycemia, whereas pharmacological inhibition of O-GlcNAc transferase (OGT) restored these molecular changes. Together, our results demonstrate O-GlcNAc mediated sensitivity of chromatin to nutrient status, and indicate how metabolic perturbations could affect gene expression during neurodevelopment.
      Keywords: Stem Cells, Chromatin & Epigenetics, Development
      PubDate: 2022-04-25T06:15:38-07:00
      DOI: 10.26508/lsa.202201385
      Issue No: Vol. 5, No. 8 (2022)
       
  • Map7D2 and Map7D1 facilitate microtubule stabilization through distinct
           mechanisms in neuronal cells

    • Authors: Kikuchi, K; Sakamoto, Y, Uezu, A, Yamamoto, H, Ishiguro, K.-i, Shimamura, K, Saito, T, Hisanaga, S.-i, Nakanishi, H.
      Abstract: Microtubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. We show that the MAP7 family protein Map7D2 stabilizes MTs to control cell motility and neurite outgrowth. Map7D2 directly bound to MTs through its N-terminal half and stabilized MTs in vitro. Map7D2 localized prominently to the centrosome and partially on MTs in mouse N1-E115 neuronal cells, which expresses two of the four MAP7 family members, Map7D2 and Map7D1. Map7D2 loss decreased the resistance to the MT-destabilizing agent nocodazole without affecting acetylated/detyrosinated stable MTs, suggesting that Map7D2 stabilizes MTs via direct binding. In addition, Map7D2 loss increased the rate of random cell migration and neurite outgrowth, presumably by disturbing the balance between MT stabilization and destabilization. Map7D1 exhibited similar subcellular localization and gene knockdown phenotypes to Map7D2. However, in contrast to Map7D2, Map7D1 was required for the maintenance of acetylated stable MTs. Taken together, our data suggest that Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms in cell motility and neurite outgrowth.
      Keywords: Cell Biology
      PubDate: 2022-04-25T06:15:38-07:00
      DOI: 10.26508/lsa.202201390
      Issue No: Vol. 5, No. 8 (2022)
       
  • Adipose tissue-specific ablation of Ces1d causes metabolic dysregulation
           in mice

    • Authors: Li, G; Li, X, Yang, L, Wang, S, Dai, Y, Fekry, B, Veillon, L, Tan, L, Berdeaux, R, Eckel-Mahan, K, Lorenzi, P. L, Zhao, Z, Lehner, R, Sun, K.
      Abstract: Carboxylesterase 1d (Ces1d) is a crucial enzyme with a wide range of activities in multiple tissues. It has been reported to localize predominantly in ER. Here, we found that Ces1d levels are significantly increased in obese patients with type 2 diabetes. Intriguingly, a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce a unique set of fatty acids. We further revealed that adipose tissue–specific Ces1d knock-out (FKO) mice gained more body weight with increased fat mass during a high fat-diet challenge. The FKO mice exhibited impaired glucose and lipid metabolism and developed exacerbated liver steatosis. Mechanistically, deficiency of Ces1d induced abnormally large lipid droplet deposition in the adipocytes, causing ectopic accumulation of triglycerides in other peripheral tissues. Furthermore, loss of Ces1d diminished the circulating free fatty acids serving as signaling molecules to trigger the epigenetic regulations of energy metabolism via lipid-sensing transcriptional factors, such as HNF4α. The metabolic disorders induced an unhealthy microenvironment in the metabolically active tissues, ultimately leading to systemic insulin resistance.
      Keywords: Metabolism, Cell Biology, Chemical Biology
      PubDate: 2022-04-22T09:30:20-07:00
      DOI: 10.26508/lsa.202101209
      Issue No: Vol. 5, No. 8 (2022)
       
  • The value of genotype-specific reference for transcriptome analyses in
           barley

    • Authors: Guo, W; Coulter, M, Waugh, R, Zhang, R.
      Abstract: It is increasingly apparent that although different genotypes within a species share "core" genes, they also contain variable numbers of "specific" genes and different structures of "core" genes that are only present in a subset of individuals. Using a common reference genome may thus lead to a loss of genotype-specific information in the assembled Reference Transcript Dataset (RTD) and the generation of erroneous, incomplete or misleading transcriptomics analysis results. In this study, we assembled genotype-specific RTD (sRTD) and common reference–based RTD (cRTD) from RNA-seq data of cultivated Barke and Morex barley, respectively. Our quantitative evaluation showed that the sRTD has a significantly higher diversity of transcripts and alternative splicing events, whereas the cRTD missed 40% of transcripts present in the sRTD and it only has ~70% accurate transcript assemblies. We found that the sRTD is more accurate for transcript quantification as well as differential expression analysis. However, gene-level quantification is less affected, which may be a reasonable compromise when a high-quality genotype-specific reference is not available.
      Keywords: Genomics & Functional Genomics, Plant Science, Systems & Computational Biology
      PubDate: 2022-04-22T09:30:20-07:00
      DOI: 10.26508/lsa.202101255
      Issue No: Vol. 5, No. 8 (2022)
       
  • The miR-26 family regulates early B cell development and transformation

    • Authors: Hutter, K; Lindner, S. E, Kurschat, C, Rülicke, T, Villunger, A, Herzog, S.
      Abstract: MiRNAs are small noncoding RNAs that promote the sequence-specific repression of their respective target genes, thereby regulating diverse physiological as well as pathological processes. Here, we identify a novel role of the miR-26 family in early B cell development. We show that enhanced expression of miR-26 family members potently blocks the pre-B to immature B cell transition, promotes pre-B cell expansion and eventually enables growth factor independency. Mechanistically, this is at least partially mediated by direct repression of the tumor-suppressor Pten, which consequently enhances PI3K-AKT signaling. Conversely, limiting miR-26 activity in a more physiological loss-of-function approach counteracts proliferation and enhances pre-B cell differentiation in vitro as well as in vivo. We therefore postulate a rheostat-like role for the miR-26 family in progenitor B cells, with an increase in mature miR-26 levels signaling cell expansion, and facilitating pre-B to the immature B cell progression when reduced.
      Keywords: Immunology, Molecular Biology, Cancer
      PubDate: 2022-04-22T09:30:20-07:00
      DOI: 10.26508/lsa.202101303
      Issue No: Vol. 5, No. 8 (2022)
       
  • Phospholipids alter activity and stability of mitochondrial membrane-bound
           ubiquitin ligase MARCH5

    • Authors: Merklinger, L; Bauer, J, Pedersen, P. A, Damgaard, R. B, Morth, J. P.
      Abstract: Mitochondrial homeostasis is tightly controlled by ubiquitination. The mitochondrial integral membrane ubiquitin ligase MARCH5 is a crucial regulator of mitochondrial membrane fission, fusion, and disposal through mitophagy. In addition, the lipid composition of mitochondrial membranes can determine mitochondrial dynamics and organelle turnover. However, how lipids influence the ubiquitination processes that control mitochondrial homeostasis remains unknown. Here, we show that lipids common to the mitochondrial membranes interact with MARCH5 and affect its activity and stability depending on the lipid composition in vitro. As the only one of the tested lipids, cardiolipin binding to purified MARCH5 induces a significant decrease in thermal stability, whereas stabilisation increases the strongest in the presence of phosphatidic acid. Furthermore, we observe that the addition of lipids to purified MARCH5 alters the ubiquitination pattern. Specifically, cardiolipin enhances auto-ubiquitination of MARCH5. Our work shows that lipids can directly affect the activity of ubiquitin ligases and suggests that the lipid composition in mitochondrial membranes could control ubiquitination-dependent mechanisms that regulate the dynamics and turnover of mitochondria.
      Keywords: Molecular Biology, Biophysics
      PubDate: 2022-04-22T09:30:20-07:00
      DOI: 10.26508/lsa.202101309
      Issue No: Vol. 5, No. 8 (2022)
       
  • Single-cell RNA-seq reveals heterogeneity in hiPSC-derived muscle
           progenitors and E2F family as a key regulator of proliferation

    • Authors: Nalbandian, M; Zhao, M, Kato, H, Jonouchi, T, Nakajima-Koyama, M, Yamamoto, T, Sakurai, H.
      Abstract: Human pluripotent stem cell-derived muscle progenitor cells (hiPSC-MuPCs) resemble fetal-stage muscle progenitor cells and possess in vivo regeneration capacity. However, the heterogeneity of hiPSC-MuPCs is unknown, which could impact the regenerative potential of these cells. Here, we established an hiPSC-MuPC atlas by performing single-cell RNA sequencing of hiPSC-MuPC cultures. Bioinformatic analysis revealed four cell clusters for hiPSC-MuPCs: myocytes, committed, cycling, and noncycling progenitors. Using FGFR4 as a marker for noncycling progenitors and cycling cells and CD36 as a marker for committed and myocyte cells, we found that FGFR4+ cells possess a higher regenerative capacity than CD36+ cells. We also identified the family of E2F transcription factors are key regulators of hiPSC-MuPC proliferation. Our study provides insights on the purification of hiPSC-MuPCs with higher regenerative potential and increases the understanding of the transcriptional regulation of hiPSC-MuPCs.
      Keywords: Stem Cells
      PubDate: 2022-04-22T06:04:43-07:00
      DOI: 10.26508/lsa.202101312
      Issue No: Vol. 5, No. 8 (2022)
       
  • SMN-deficient cells exhibit increased ribosomal DNA damage

    • Authors: Karyka, E; Berrueta Ramirez, N, Webster, C. P, Marchi, P. M, Graves, E. J, Godena, V. K, Marrone, L, Bhargava, A, Ray, S, Ning, K, Crane, H, Hautbergue, G. M, El-Khamisy, S. F, Azzouz, M.
      Abstract: Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. SMN is a multifunctional protein that is implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention is being paid to the role of SMN in the maintenance of DNA integrity. DNA damage and genome instability have been linked to a range of neurodegenerative diseases. The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. Instability in rDNA has been associated with cancer, premature ageing syndromes, and a number of neurodegenerative disorders. Here, we report that SMN-deficient cells exhibit increased rDNA damage leading to impaired ribosomal RNA synthesis and translation. We also unravel an interaction between SMN and RNA polymerase I. Moreover, we uncover an spinal muscular atrophy motor neuron-specific deficiency of DDX21 protein, which is required for resolving R-loops in the nucleolus. Taken together, our findings suggest a new role of SMN in rDNA integrity.
      Keywords: Neuroscience
      PubDate: 2022-04-19T09:50:38-07:00
      DOI: 10.26508/lsa.202101145
      Issue No: Vol. 5, No. 8 (2022)
       
  • LuminoCell: a versatile and affordable platform for real-time monitoring
           of luciferase-based reporters

    • Authors: Weissova, K; Fafilek, B, Radaszkiewicz, T, Celiker, C, Machackova, P, Cechova, T, Sebestikova, J, Hampl, A, Bryja, V, Krejci, P, Barta, T.
      Abstract: Luciferase reporter assays represent a simple and sensitive experimental system in cell and molecular biology to study multiple biological processes. However, the application of these assays is often limited by the costs of conventional luminometer instruments and the versatility of their use in different experimental conditions. Therefore, we aimed to develop a small, affordable luminometer allowing continuous measurement of luciferase activity, designed for inclusion into various kinds of tissue culture incubators. Here, we introduce LuminoCell—an open-source platform for the construction of an affordable, sensitive, and portable luminometer capable of real-time monitoring in-cell luciferase activity. The LuminoCell costs $40, requires less than 1 h to assemble, and it is capable of performing real-time sensitive detection of both magnitude and duration of the activity of major signalling pathways in cell cultures, including receptor tyrosine kinases (EGF and FGF), WNT/β-catenin, and NF-B. In addition, we show that the LuminoCell is suitable to be used in cytotoxicity assays as well as for monitoring periodic circadian gene expression.
      Keywords: Methods & Resources, Molecular Biology, Cell Biology
      PubDate: 2022-04-19T09:50:38-07:00
      DOI: 10.26508/lsa.202201421
      Issue No: Vol. 5, No. 8 (2022)
       
  • Tricalbin proteins regulate plasma membrane phospholipid homeostasis

    • Authors: Thomas, F. B; Omnus, D. J, Bader, J. M, Chung, G. H, Kono, N, Stefan, C. J.
      Abstract: The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the ER and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain incomplete. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also control the PM targeting of the known phosphatidylserine effector Pkc1 upon heat-induced stress. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We propose that phospholipid regulation is an ancient essential function of E-Syt family members required for PM integrity.
      Keywords: Molecular Biology, Cell Biology
      PubDate: 2022-04-19T09:50:38-07:00
      DOI: 10.26508/lsa.202201430
      Issue No: Vol. 5, No. 8 (2022)
       
  • Evaluation of the correctable decoding sequencing as a new powerful
           strategy for DNA sequencing

    • Authors: Cheng, C; Xiao, P.
      Abstract: Next-generation sequencing (NGS) promises to revolutionize precision medicine, but the existing sequencing technologies are limited in accuracy. To overcome this limitation, we propose the correctable decoding sequencing strategy, which is a duplex sequencing protocol with conservative theoretical error rates of 0.0009%. This rate is lower than that for Sanger sequencing. Here, we simulate the sequencing reactions by the self-developed software, and find that this approach has great potential in NGS in terms of sequence decoding, reassembly, error correction, and sequencing accuracy. Besides, this approach can be compatible with most SBS-based sequencing platforms, and also has the ability to compensate for some of the shortcomings of NGS platforms, thereby broadening its application for researchers. Hopefully, it can provide a powerful new protocol that can be used as an alternative to the existing NGS platforms, enabling accurate identification of rare mutations in a variety of applications in biology and medicine.
      Keywords: Methods & Resources
      PubDate: 2022-04-14T14:32:39-07:00
      DOI: 10.26508/lsa.202101294
      Issue No: Vol. 5, No. 8 (2022)
       
  • Polycomb group ring finger protein 6 suppresses Myc-induced
           lymphomagenesis

    • Authors: Tanaskovic, N; Dalsass, M, Filipuzzi, M, Ceccotti, G, Verrecchia, A, Nicoli, P, Doni, M, Olivero, D, Pasini, D, Koseki, H, Sabo, A, Bisso, A, Amati, B.
      Abstract: Max is an obligate dimerization partner for the Myc transcription factors and for several repressors, such as Mnt, Mxd1-4, and Mga, collectively thought to antagonize Myc function in transcription and oncogenesis. Mga, in particular, is part of the variant Polycomb group repressive complex PRC1.6. Here, we show that ablation of the distinct PRC1.6 subunit Pcgf6–but not Mga–accelerates Myc-induced lymphomagenesis in Eµ-myc transgenic mice. Unexpectedly, however, Pcgf6 loss shows no significant impact on transcriptional profiles, in neither pre-tumoral B-cells, nor lymphomas. Altogether, these data unravel an unforeseen, Mga- and PRC1.6-independent tumor suppressor activity of Pcgf6.
      Keywords: Cancer
      PubDate: 2022-04-14T14:32:39-07:00
      DOI: 10.26508/lsa.202101344
      Issue No: Vol. 5, No. 8 (2022)
       
 
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