Featured
-
-
Article
| Open AccessSpecificity, synergy, and mechanisms of splice-modifying drugs
Two small-molecule drugs, risdiplam and branaplam, have been developed for treating spinal muscular atrophy. Here the authors develop quantitative modeling methods for the sequence-specific and concentration-dependent effects of these and other splice-modifying drugs.
- Yuma Ishigami
- , Mandy S. Wong
- & Justin B. Kinney
-
Article
| Open AccessTopBP1 utilises a bipartite GINS binding mode to support genome replication
Effective and regulated activation of the Mcm2-7 helicase underlies faithful genome replication. Here the authors reveal mechanistic detail how the pre-loading complex proteins TopBP1 and GINS interact and, thus, how the helicase activator GINS loads on Mcm2-7 during replication origin firing.
- Matthew Day
- , Bilal Tetik
- & Dominik Boos
-
Article
| Open AccessDevelopment of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies
Sickle cell disease (SCD) and β-thalassemia (BT) are globally prevalent inherited blood disorders but, despite extensive research, no ex vivo system exists for SCD and BT. Here, the authors generate pathophysiologically relevant erythroid progenitor models of SCD and BT.
- Pragya Gupta
- , Sangam Giri Goswami
- & Sivaprakash Ramalingam
-
Article
| Open AccessInterplay between coding and non-coding regulation drives the Arabidopsis seed-to-seedling transition
Seed germination in plants is a tightly controlled process relying on translation of stored RNAs. Here, Tremblay et al. show that nascent transcriptome and epigenome reprogramming are detected from initial stages of germination.
- Benjamin J. M. Tremblay
- , Cristina P. Santini
- & Julia I. Qüesta
-
Article
| Open AccessA distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study
Alternative polyadenylation (APA) can play a key role in cancer initiation and progression. Here, the authors conducted a comprehensive pan-cancer APA TWAS analysis and discovered a distinct class of APA-mediated cancer susceptibility genes across 22 cancer types.
- Hui Chen
- , Zeyang Wang
- & Lei Li
-
Article
| Open AccessCellular reprogramming in vivo initiated by SOX4 pioneer factor activity
Upon physiological injury, hepatocytes transdifferentiate into biliary epithelial cells, a process involving molecular rewiring. Here, authors show that Sox4 organizes the early steps, acting as a pioneer factor to decommission hepatocyte enhancers and open chromatin around biliary genes.
- Takeshi Katsuda
- , Jonathan H. Sussman
- & Ben Z. Stanger
-
Article
| Open AccessTransient disome complex formation in native polysomes during ongoing protein synthesis captured by cryo-EM
Direct visualization of short-lived intermediates during active protein synthesis remains challenging. Here, the authors structurally capture transient translation intermediates to uncover temporary disome formation during ribosome collisions.
- Timo Flügel
- , Magdalena Schacherl
- & Christian M. T. Spahn
-
Article
| Open AccessSingle-molecule RNA sizing enables quantitative analysis of alternative transcription termination
The development of RNA technologies demands accurate assessment of transcript size and heterogeneity. Here, authors report a nanopore-based approach to study full-length RNA transcripts at the single-molecule level, identify premature transcription termination and study rolling-circle transcription.
- Gerardo Patiño-Guillén
- , Jovan Pešović
- & Ulrich Felix Keyser
-
Article
| Open AccessImplications of the three-dimensional chromatin organization for genome evolution in a fungal plant pathogen
The spatial organization of eukaryotic genomes is linked to their biological functions. Here, the authors study the 3D genome organization of the phytopathogenic fungus Verticillium dahliae, revealing links to evolutionary features conserved throughout the Verticillium genus.
- David E. Torres
- , H. Martin Kramer
- & Bart P. H. J. Thomma
-
Article
| Open AccessBacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism
The mechanisms underlying adaptation of bacteria to changing environmental conditions remain poorly understood. Here, the authors show bacteria using lysine acetylation of transcriptional regulators to adjust gene expression to changing conditions.
- Magdalena Kremer
- , Sabrina Schulze
- & Michael Lammers
-
Article
| Open AccessCbp1 and Cren7 form chromatin-like structures that ensure efficient transcription of long CRISPR arrays
CRISPR arrays form the physical memory of prokaryotic adaptive immune systems by incorporating viral DNA sequences as spacers. Here, Blombach et al. show that transcription factor Cbp1 recruits chromatin protein Cren7 at CRISPR arrays, forming ‘chimeric’ chromatin-like structures that regulate expression of long CRISPR arrays in Sulfolobales archaea.
- Fabian Blombach
- , Michal Sýkora
- & Finn Werner
-
Article
| Open AccessStalled translation by mitochondrial stress upregulates a CNOT4-ZNF598 ribosomal quality control pathway important for tissue homeostasis
Ribosome associated quality control (RQC) is a new area of biological investigation with emerging connection to a broad range of diseases. Here authors show that mitochondrial stress can upregulate a new RQC pathway important for tissue homeostasis.
- Ji Geng
- , Shuangxi Li
- & Bingwei Lu
-
Article
| Open AccessDecryption of sequence, structure, and functional features of SINE repeat elements in SINEUP non-coding RNA-mediated post-transcriptional gene regulation
Here the authors elucidate structure-function relationships of SINEUPs, antisense long non-coding RNAs that through SINE repeat elements positively regulate protein translation of mRNAs they pair with. SINEUP’s functional domains do not share common ancestors.
- Harshita Sharma
- , Matthew N. Z. Valentine
- & Piero Carninci
-
Article
| Open AccessOncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner
Here the authors report that oncogenic c-Myc induces replication stress via increasing the amount of cohesins bound to chromatin at CTCF sites.
- Silvia Peripolli
- , Leticia Meneguello
- & Robertus A. M. de Bruin
-
Article
| Open AccessOrthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells
The lack of control over Cas13 activity has limited its utility. Here the authors report Control of RNA with Inducible SpliT CAs13 Orthologs and Exogenous Ligands (CRISTAL), controlled by orthogonal split inducible Cas13 effectors that can be turned ON or OFF, providing precise temporal control.
- Yage Ding
- , Cristina Tous
- & Wilson W. Wong
-
Article
| Open AccessStructure of the recombinant RNA polymerase from African Swine Fever Virus
Pilotto and colleagues produce recombinant and catalytically active RNA polymerase (RNAP) from African Swine Fever Virus. Cryo-EM structures of RNAP with closed and open clamp conformations are presented along with in vitro transcription assays, yielding distinct functional conclusions.
- Simona Pilotto
- , Michal Sýkora
- & Finn Werner
-
Article
| Open AccessMeiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair
Aberrant expression of Synaptonemal complex protein 2 (SYCP2) in breast and ovarian cancers is associated with resistance to drugs targeting the DNA damage response. Here the authors show that SYCP2 confers drug resistance by promoting R-loop formation during transcription-coupled homologous recombination.
- Yumin Wang
- , Boya Gao
- & Li Lan
-
Article
| Open AccessIdentification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages
The diverse functional roles of ribozymes (RNAs with enzymatic activity) continue to be uncovered. Here, the authors identify and characterize a subgroup of minimal hepatitis delta virus (HDV)-like ribozymes – termed Theta ribozymes -, which they show process viral tRNA transcripts, and appearing crucial for lytic gene expression in recoded phages.
- Kasimir Kienbeck
- , Lukas Malfertheiner
- & Roland K. O. Sigel
-
Article
| Open AccessA transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration
The etiology of TDP-43 proteinopathy in ALS and FTD is complex. Here, the authors show that prior to disease onset in the rNLS8 mouse model, cortex neurons elicit a transient increase in protective chaperones that combat TDP-43 aggregation.
- Rebecca San Gil
- , Dana Pascovici
- & Adam K. Walker
-
Article
| Open AccessDomain-inlaid Nme2Cas9 adenine base editors with improved activity and targeting scope
Nme2Cas9 has been well established as a genome editing platform. Here the authors engineer Nme2Cas9 to further increase the activity and targeting scope of compact Nme2Cas9 base editors and validate domain-inlaid Nme2-ABEs for single-AAV delivery in vivo.
- Nathan Bamidele
- , Han Zhang
- & Erik J. Sontheimer
-
Article
| Open AccessChp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis
Here the authors discover a dedicated ribosome-associated chaperone, Chp1, that assists in the challenging biogenesis of eukaryotic translation elongation factor 1A (eEF1A) by cotranslationally stabilizing the growing GTPase domain of eEF1A.
- Melania Minoia
- , Jany Quintana-Cordero
- & Claes Andréasson
-
Article
| Open AccessTrabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes
The antitumor drug trabectedin is more toxic to DNA-repair-proficient cells. Here the authors show that this is caused by persistent DNA breaks induced from an abortive repair reaction and develop “TRABI-Seq” to map the breaks to transcribed regions of the genome. Trabectedin may thus be used as a diagnostic and therapeutic in precision oncology.
- Kook Son
- , Vakil Takhaveev
- & Orlando D. Schärer
-
Article
| Open AccessHigh resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing
Advancements in spatial transcriptomics technologies have enabled the analysis of gene expression at cellular resolution in situ. The authors applied direct RNA hybridization-based in situ sequencing (dRNA HybISS) and developed a computational tool, CellScopes, to study gene expression in mouse kidneys, identifying cellular changes and interactions during injury and repair.
- Haojia Wu
- , Eryn E. Dixon
- & Benjamin D. Humphreys
-
Article
| Open AccessAdipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape
Adipose tissue (AT) inflammation is strongly associated with obesity and constitutes an obesogenic memory upon weight loss. Here, the authors show that intermittent fasting leads to an adipocyte p53-signaling dependent emergence of lipid-associated macrophages in visceral AT of obese mice which limits the systemic fasting response.
- Isabel Reinisch
- , Helene Michenthaler
- & Andreas Prokesch
-
Article
| Open AccessMultigenerational paternal obesity enhances the susceptibility to male subfertility in offspring via Wt1 N6-methyladenosine modification
The mechanisms through which multigenerational paternal obesity affects spermatogenesis in offspring remain poorly understood. Here, the authors show that it affects Wt1 m6A modifications, decreasing the fertility of offspring.
- Yong-Wei Xiong
- , Hua-Long Zhu
- & Hua Wang
-
Article
| Open AccessMolecular basis of VEGFR1 autoinhibition at the plasma membrane
Spontaneous activation of VEGFRs is a hallmark of diabetes and several cancers. Here, the authors show how in VEGFR1 a juxtamembrane segment connecting the catalytic and ligand-binding domains of the receptor can prevent its spontaneous activation.
- Manas Pratim Chakraborty
- , Diptatanu Das
- & Rahul Das
-
Article
| Open AccessUltrastructure of macromolecular assemblies contributing to bacterial spore resistance revealed by in situ cryo-electron tomography
Bacterial endospores are among the most resilient forms of life. Here, authors reveal ultrastructural details of the spore chromosome and the multiprotein, multilayered extracellular coat, shedding light on mechanisms contributing to spore resistance.
- Elda Bauda
- , Benoit Gallet
- & Cecile Morlot
-
Article
| Open AccessProteome-Wide Identification of RNA-dependent proteins and an emerging role for RNAs in Plasmodium falciparum protein complexes
Ribonucleoprotein complexes play fundamental roles in many cellular processes. Here, the authors used a proteome-wide approach, R-DeeP, to identify protein complexes associated with RNA in the deadliest human malaria parasite, Plasmodium falciparum.
- Thomas Hollin
- , Steven Abel
- & Karine G. Le Roch
-
Article
| Open AccessThe transcriptional regulatory network modulating human trophoblast stem cells to extravillous trophoblast differentiation
Extravillous trophoblasts are pivotal in placental invasion and artery remodeling. Here the authors report stage-specific transcriptional regulators and their sequential roles in guiding proper trophoblast differentiation.
- Mijeong Kim
- , Yu Jin Jang
- & Jonghwan Kim
-
Article
| Open AccessStructural role for DNA Ligase IV in promoting the fidelity of non-homologous end joining
Nonhomologous end joining (NHEJ), the primary pathway of vertebrate DNA double strand-break (DSB) repair, directly re-ligates broken DNA ends with minimal errors. In this study, the authors identify structural interactions of the NHEJ-specific DNA Ligase IV (Lig4) that prioritize ligation and promote NHEJ fidelity.
- Benjamin M. Stinson
- , Sean M. Carney
- & Joseph J. Loparo
-
Article
| Open AccessNutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control
The quality of germline mitochondria is essential for producing healthy oocytes. Here, Ng, Chan and Pek report a stable intron that modulates germline mitochondrial quality control during fasting, heat stress and aging.
- Annabel Qi En Ng
- , Seow Neng Chan
- & Jun Wei Pek
-
Article
| Open AccessMatrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions
Alterations in proteins within nuclear compartments often lead to changes in chromosomal architecture. Here, using acute targeted protein degradation, the authors reveal that the nuclear complex protein Matrin3 directly mediates differentiation through stabilizing chromatin loop domain interactions.
- Tianxin Liu
- , Qian Zhu
- & Stuart H. Orkin
-
Article
| Open AccessProtein thermal sensing regulates physiological amyloid aggregation
Cells form non-pathological amyloids to survive stressful conditions. Marijan et al. show that heat shock-induced aggregation is self-regulated by protein stability, with high-ordered motifs acting as thermo-switches that control amyloidogenesis.
- Dane Marijan
- , Evgenia A. Momchilova
- & Timothy E. Audas
-
Article
| Open AccessRegulation of TRI5 expression and deoxynivalenol biosynthesis by a long non-coding RNA in Fusarium graminearum
The fungus Fusarium graminearum produces a toxin, deoxynivalenol (DON), that can be found in cereal grains and processed food or feed. Here, Huang et al. study the regulation of DON biosynthesis and show that transcription factors TRI6 and TRI10 regulate each other’s expression and that of a long non-coding RNA which, in turn, downregulates a DON biosynthesis gene.
- Panpan Huang
- , Xiao Yu
- & Cong Jiang
-
Article
| Open AccessPredicting DNA structure using a deep learning method
In this work, the authors report a deep learning method, Deep DNAshape, to predict the influence of flanking regions on three-dimensional DNA structure and in structural readout mechanisms of protein-DNA binding.
- Jinsen Li
- , Tsu-Pei Chiu
- & Remo Rohs
-
Article
| Open AccessTracing back primed resistance in cancer via sister cells
Transcriptional cell states can drive treatment resistance in cancer. Here, the authors develop ReSisTrace to predict cell states that are primed to resist ovarian cancer treatment and validate their findings using small molecule inhibitors.
- Jun Dai
- , Shuyu Zheng
- & Anna Vähärautio
-
Article
| Open AccessASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97
VCP/p97 is identified as a co-factor to the fusion oncoprotein ASPSCR1::TFE3. They co-localize on chromatin, co-dependent for enhancer looping and transcriptional regulation in alveolar soft part sarcomas and Xp11- rearranged renal cell carcinomas.
- Amir Pozner
- , Li Li
- & Kevin B. Jones
-
Article
| Open AccessG-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis
G-quadruplexes (G4s) can recruit transcription factors to activate genes. Here, the authors revealed that G4s drive molecular motility in phase-separated condensates of MAZ and coactivators, leading to activated CCND1 expression in liver cancer.
- Wenmeng Wang
- , Dangdang Li
- & Guangchao Sui
-
Article
| Open AccessThe host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
The cellular RNA polymerase II C-terminal domain is known to support transcription of influenza virus mRNAs. Here, Krischuns et al. use cell-based and in vitro approaches to demonstrate that it also plays a role in replication of the viral genome.
- Tim Krischuns
- , Benoît Arragain
- & Nadia Naffakh
-
Article
| Open AccessC2-methyladenosine in tRNA promotes protein translation by facilitating the decoding of tandem m2A-tRNA-dependent codons
Duan et al. demonstrate that the m2A modification is ubiquitous in plants and tRNA m2A37 promotes a relaxed conformation of tRNA, enhancing translation efficiency by facilitating decoding of tandem m2A-tRNA-dependent codons.
- Hong-Chao Duan
- , Chi Zhang
- & Guifang Jia
-
Article
| Open AccessANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation
The transcriptional program controlling the activation of cancer-associated fibroblasts (CAFs) remains to be elucidated. Here, the authors identify ANKRD1 as a mesenchymal-specific driver of CAF activation under negative direct control of androgen receptor, triggering AP-1 transcription factor complex activation.
- Luigi Mazzeo
- , Soumitra Ghosh
- & G. Paolo Dotto
-
Article
| Open AccessThe chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors
Replication stress represents a major threat to genome integrity of normal and cancer cells. Here, the authors find that the long non-coding RNA lncREST affects the replication stress response through interaction with nucleolin. This interaction bridges the recruitment of replication factors to stressed chromatin.
- Luisa Statello
- , José Miguel Fernandez-Justel
- & Maite Huarte
-
Article
| Open AccessTissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans
Wang et al. profile age-dependent miRNAomic changes in worm tissues and extracellular vesicles (EVs). They show that ageing controls miRNAs in a tissue-specific manner and their findings further suggest a complex EV-mediated miRNA trafficking network across tissues.
- Xueqing Wang
- , Quanlong Jiang
- & Yidong Shen
-
Article
| Open AccessRan-GTP assembles a specialized spindle structure for accurate chromosome segregation in medaka early embryos
Mitotic spindle assembles in each blastomere to segregate duplicated chromosomes during cleavage of the fertilized egg. Here, the authors establish functional assays in fish embryos and find that Ran-GTP assembles a microtubule network at the metaphase spindle center that is essential for chromosome segregation.
- Ai Kiyomitsu
- , Toshiya Nishimura
- & Tomomi Kiyomitsu
-
Article
| Open AccessAnti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages
CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. Here the authors show an anti-drive mosquito strain that prevents the spread and collapse of a population suppression gene drive in laboratory Anopheles mosquito large cage trials in complex ecological and behavioral conditions.
- Rocco D’Amato
- , Chrysanthi Taxiarchi
- & Ruth Müller
-
Article
| Open AccessHRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1
Argonaute proteins are loaded with small RNAs to confer target RNA specificity and proper gene silencing. Here, the authors establish that HRDE-2 recruits the unloaded nuclear Argonaute HRDE-1 to germ granules to facilitate correct small RNA loading.
- Shihui Chen
- & Carolyn M. Phillips
-
Article
| Open AccessMultiplexed screening reveals how cancer-specific alternative polyadenylation shapes tumor growth in vivo
Dysregulation of alternative polyadenylation (APA) is associated with poor prognosis in cancer but its functional role is less clear. Here, the authors develop a CRISPR-Cas9- based screen to determine the effects of different APA events on melanoma growth in mouse models.
- Austin M. Gabel
- , Andrea E. Belleville
- & Robert K. Bradley
-
Article
| Open AccessUbiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates
Upon cold exposure, two types of thermogenic fat cells, brown and beige adipocytes, are sequentially activated. Here, the authors show that E3 ubiquitin ligase RNF20 coordinates the sequential thermogenic activation through fat depot specific substrates.
- Yong Geun Jeon
- , Hahn Nahmgoong
- & Jae Bum Kim
-
Article
| Open AccessFLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress
Recombination is essential for life. Here, the authors characterize FLIP as a novel regulator of the key recombination protein RAD51’s functions. FLIP loss caused marked sensitivity to DNA damage, increased DNA breakage and defective replication.
- Jessica D. Tischler
- , Hiroshi Tsuchida
- & Richard O. Adeyemi
Browse broader subjects
Browse narrower subjects
- Cell division
- Chromatin
- Chromosomes
- CRISPR-Cas systems
- DNA damage and repair
- DNA metabolism
- DNA recombination
- DNA replication
- Epigenetics
- Non-coding RNAs
- Nuclear organization
- Post-translational modifications
- Protein folding
- Proteolysis
- Proteomics
- Riboswitches
- Ribozymes
- RNA metabolism
- RNAi
- Single-molecule biophysics
- Transcription
- Transcriptomics
- Translation
- Transposition