Molecular biology articles within Nature Communications

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  • Article
    | Open Access

    Alternative splicing of influenza A virus (IAV) M transcript is regulated by hnRNP K and NS1-BP, but mechanistic details are unknown. Here, Thompson et al. show how hnRNP K and NS1-BP bind M mRNA and that these proteins regulate splicing of host transcripts in both the absence and presence of IAV infection.

    • Matthew G. Thompson
    • , Raquel Muñoz-Moreno
    •  & Kristen W. Lynch

  • Article
    | Open Access

    During DNA replication, replicative helicases play an essential role for DNA unwinding to occur. Here the authors find that bacteriophage T7 helicase is also involved in replication re-initiation by interacting with a non-replicating DNAP and increasing unwinding rate.

    • Bo Sun
    • , Anupam Singh
    •  & Michelle D. Wang

  • Article
    | Open Access

    Chromatin-associated protein complexes play a critical role in the regulation of gene expression in health and disease. Here, the authors describe a sensitive mass spectrometry-based method to monitor the dynamic interactions of endogenous chromatin-associated protein complexes in clinical samples.

    • Evangelia K. Papachristou
    • , Kamal Kishore
    •  & Jason S. Carroll

  • Article
    | Open Access

    Mutations in the RNA component TERC can cause telomerase dysfunction but the underlying mechanisms are largely unknown. Here, the authors show that RNA-binding protein HuR regulates telomerase function by enhancing the methylation of TERC, which is impaired by several disease-relevant TERC mutations.

    • Hao Tang
    • , Hu Wang
    •  & Wengong Wang

  • Article
    | Open Access

    The moth Plutella xylostella during its larval stage is the host of the endoparasitic wasp Cotesia vestalis. Here the authors show that the parasitoids deliver microRNAs to their hosts through their symbiotic virus and specialized cells leading to induced developmental delay.

    • Zhi-zhi Wang
    • , Xi-qian Ye
    •  & Xue-xin Chen

  • Article
    | Open Access

    The precise timing of neurodevelopmental splicing switches and the underlying regulatory mechanisms remain poorly understood. This study identifies two major waves of developmental switches under the control of distinct combinations of RNA-binding proteins in central and peripheral nervous systems.

    • Sebastien M. Weyn-Vanhentenryck
    • , Huijuan Feng
    •  & Chaolin Zhang

  • Article
    | Open Access

    SETBP1 variants occur as somatic mutations in several malignancies and as de novo germline mutations in developmental disorders. Here the authors provide evidence that SETBP1 binds to gDNA in AT-rich promoter regions to promote target gene upregulation, indicating SETBP1 functions directly to regulate transcription.

    • Rocco Piazza
    • , Vera Magistroni
    •  & Carlo Gambacorti-Passerini

  • Article
    | Open Access

    Base editing allows the precise introduction of point mutations into cellular DNA without requiring double-stranded DNA breaks or homology-directed repair, which is inefficient in postmitotic cells. Here the authors demonstrate in vivo base editing of post-mitotic somatic cells in the postnatal mouse inner ear with physiological outcomes.

    • Wei-Hsi Yeh
    • , Hao Chiang
    •  & David R. Liu

  • Article
    | Open Access

    The p53-binding protein 1 (53BP1) regulates the choice of the DNA double-strand break repair pathway. Here the authors present the crystal structure of Tudor-interacting repair regulator (TIRR) bound to the 53BP1 tandem Tudor domain, which reveals how TIRR blocks H4K20me2 binding to 53BP1 Tudor and functionally differs from its paralog Nudt16.

    • Yaxin Dai
    • , Aili Zhang
    •  & Zheng Zhou

  • Article
    | Open Access

    Steatosis is characterized by initial accumulation of lipids, followed by inflammation and ultimately fibrosis. Here the authors show that the histone demethylase Plant Homeodomain Finger 2 protects liver form steatosis progression by acting as a co-activator of ChREBP, thus, favouring lipid accumulation without inflammation.

    • Julien Bricambert
    • , Marie-Clotilde Alves-Guerra
    •  & Renaud Dentin

  • Article
    | Open Access

    R2TP is an HSP90 co-chaperone composed of an RPAP3-PIH1D1 heterodimer, which binds two essential AAA+ ATPases RUVBL1/RUVBL2. Here authors use a structural approach to study RPAP3 and find an RPAP3-like protein (SPAG1) which also forms a co-chaperone complex with PIH1D2 and RUVBL1/2 enriched in testis.

    • Chloé Maurizy
    • , Marc Quinternet
    •  & Edouard Bertrand

  • Article
    | Open Access

    Diffuse intrinsic pontine gliomas exhibit a characteristic mutation of lysine 27 to methionine (K27M) in genes encoding histone H3.3. Here the authors show that the H3.3K27M mutation imposes a specific pattern of H3.3K27 methylation by altering the target search dynamics of PcG proteins.

    • Roubina Tatavosian
    • , Huy Nguyen Duc
    •  & Xiaojun Ren

  • Article
    | Open Access

    Calcium-calmodulin-dependent protein kinase II (CaMKII) is well known for its roles in synaptic plasticity. Using a series of molecular replacement experiments, the authors show that the kinase function of CaMKII is required for long-term plasticity and basal AMPA receptor-mediated transmission.

    • Salvatore Incontro
    • , Javier Díaz-Alonso
    •  & Roger A. Nicoll

  • Article
    | Open Access

    Here the authors show that a large fraction of the tissue-specific methylation pattern is generated postnatally. These changes, which occur in response to hormone signaling, appear to play a major role in the regulation of gene expression and tissue maturation in the liver.

    • Yitzhak Reizel
    • , Ofra Sabag
    •  & Howard Cedar

  • Article
    | Open Access

    Invadosomes degrade extracellular matrix and facilitate cell invasion but their molecular composition is not fully understood. Here, the authors combine laser capture and mass spectrometry to map the proteome of invadosomes, showing that they rely on internal translational activity to maintain their structure.

    • Zakaria Ezzoukhry
    • , Elodie Henriet
    •  & Frédéric Saltel

  • Article
    | Open Access

    Myotonic dystrophy (DM) type 2 is a neuromuscular pathology caused by large expansions of CCTG repeats. Here the authors find that rbFOX1 RNA binding protein binds to CCUG RNA repeats and competes with MBNL1 for the binding to CCUG repeats, releasing MBNL1 from sequestration in DM2 muscle cells.

    • Chantal Sellier
    • , Estefanía Cerro-Herreros
    •  & Nicolas Charlet-Berguerand

  • Article
    | Open Access

    The International Synthetic Yeast Sc2.0 project has built Cre recombinase sites into synthetic chromosomes, enabling rapid genome evolution. Here the authors demonstrate L-SCRaMbLE, a light-controlled recombinase tool with improved control over recombination events.

    • Lena Hochrein
    • , Leslie A. Mitchell
    •  & Bernd Mueller-Roeber

  • Article
    | Open Access

    Intron retention (IR) can increase protein diversity and function, and yet unregulated IR may be detrimental to cellular health. This study shows that aberrant IR occurs in ALS and finds nuclear loss of an RNA-binding protein called SFPQ as a new molecular hallmark in this devastating condition.

    • Raphaelle Luisier
    • , Giulia E. Tyzack
    •  & Rickie Patani

  • Article
    | Open Access

    Native-like soluble HIV envelope (Env) trimers are potential vaccine immunogens, and elimination of furin-dependence could provide a DNA-based alternative. Here, Sarkar et al. show that a cleavage-independent Env construct recapitulates the architecture and glycosylation of the native cleaved trimer.

    • Anita Sarkar
    • , Shridhar Bale
    •  & Ian A. Wilson

  • Article
    | Open Access

    Very little is known regarding the molecular mechanisms involved in gastric cancer development. Here the authors show estrogen-related receptor gamma (ESRRG) is a tumor suppressor in gastric cancer and suggest the mechanism of this tumor suppression function involves the inhibition of Wnt signaling.

    • Myoung-Hee Kang
    • , Hyunji Choi
    •  & Yun-Yong Park

  • Review Article
    | Open Access

    CRISPR has rapidly become an indispensable tool for biological research. Here Mazhar Adli reviews the current toolbox for editing and manipulating the genome and looks toward future developments in this fast moving field.

    • Mazhar Adli

  • Article
    | Open Access

    CRISPR interference (CRISPRi) is a method for targeted silencing of transcription that requires the coexpression of protein dCas9 and a customized guide RNA. Here, Cui et al. show that certain guide RNAs induce toxicity in E. coli, and provide design rules to minimize off-target effects.

    • Lun Cui
    • , Antoine Vigouroux
    •  & David Bikard

  • Article
    | Open Access

    Adoptive T cell therapy using an allogeneic T cell graft is an encouraging therapeutic approach in cancer, but issues such as graft-versus-host disease can hinder applicability. Here, the authors show that DOT1L inhibition or DUSP6 overexpression in T cells attenuates graft-versus-host disease but retains anti-tumour activity in mouse models.

    • Yuki Kagoya
    • , Munehide Nakatsugawa
    •  & Naoto Hirano

  • Article
    | Open Access

    Polycomb-group proteins are key regulators of transcriptional programs that maintain cell identity. Here the authors provide evidence that PCGF5, a subunit of Polycomb Repressor Complex 1, is important for the differentiation of mouse embryonic stem cells towards a neural cell fate.

    • Mingze Yao
    • , Xueke Zhou
    •  & Hongjie Yao

  • Article
    | Open Access

    Sustained spindle tension applied to sister centromeres during mitosis leads to loss of sister chromatid cohesion which is known as cohesion fatigue. Here the authors show that Aurora A-dependent phosphorylation of CENP-A at the inner centromeres protects bioriented chromosomes against cohesion fatigue.

    • Grégory Eot-Houllier
    • , Laura Magnaghi-Jaulin
    •  & Christian Jaulin

  • Article
    | Open Access

    The genetic code for amino acids is nearly universal, and among eukaryotic nuclear genomes the only known reassignments are of codon CUG in yeasts. Here, the authors identify a third independent CUG transition in budding yeasts that is still ongoing with alternative tRNAs present in the genome.

    • Tadeusz Krassowski
    • , Aisling Y. Coughlan
    •  & Kenneth H. Wolfe

  • Article
    | Open Access

    Transfer RNA modifications play critical roles in protein synthesis. Here the authors reveal the t6A37 tRNA modification is dynamically regulated by sensing intracellular CO2 concentration in mitochondria, implying metabolic regulation of protein synthesis.

    • Huan Lin
    • , Kenjyo Miyauchi
    •  & Tsutomu Suzuki

  • Article
    | Open Access

    The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms.

    • Stephen J. Pettitt
    • , Dragomir B. Krastev
    •  & Christopher J. Lord

  • Article
    | Open Access

    Cofilin is a small actin-binding protein that accelerates actin turnover by disassembling actin filaments. Here the authors present the 3.8 Å cryo-EM structure of a cofilin-decorated actin filament and discuss mechanistic implications.

    • Kotaro Tanaka
    • , Shuichi Takeda
    •  & Akihiro Narita

  • Article
    | Open Access

    NS1 of influenza A virus inhibits TRIM25 activity, which is an E3 ligase important for induction of the interferon response. Here, Koliopoulos et al. present structures of TRIM25 and NS1 and show how NS1 binding interferes with substrate recognition of TRIM25.

    • Marios G. Koliopoulos
    • , Mathilde Lethier
    •  & Katrin Rittinger

  • Article
    | Open Access

    To date, only one mutation in the gene for amyloid-beta precursor protein APP has been suggested to be protective against Alzheimer’s disease. Here, authors found using gene editing of a mutant App knock-in mouse line that deletion of the 3’UTR region is protective against amyloid-β accumulation in vivo, and subsequently identify a 52-bp element in the 3’UTR region that is responsible for this effect.

    • Kenichi Nagata
    • , Mika Takahashi
    •  & Takaomi C. Saido

  • Article
    | Open Access

    Heterochromatin protein 1a (HP1a) is thought to function downstream of transposon repression in the Drosophila female germline. Here the authors show that HP1a also functions upstream of piRNA processing by repressing splicing of piRNA precursors, predominantly at telomeric and centromeric regions.

    • Ryan Yee Wei Teo
    • , Amit Anand
    •  & Toshie Kai

  • Article
    | Open Access

    The prognosis and treatment of gastric cancer is complicated by heterogeneity. Here, the authors reveal two molecular subtypes, the mesenchymal subtype associated with poor survival and chemoresistance, and the epithelial phenotype associated with better survival and sensitivity to chemotherapy.

    • Sang Cheul Oh
    • , Bo Hwa Sohn
    •  & Ju-Seog Lee

  • Article
    | Open Access

    Small nucleolar ribonucleoprotein complexes (snoRNP) are fundamental for ribosome biogenesis. Here the authors provide insight into the 5ʹend processing of S. cerevisiae snoRNA and its important role in downstream nuclear events.

    • Pawel Grzechnik
    • , Sylwia A. Szczepaniak
    •  & Nicholas J. Proudfoot

  • Article
    | Open Access

    Recognition of intronic polyadenylation (IpA) signals can lead to expression of truncated proteins lacking C terminal domains. Analysis of 3ʹ -seq and RNA-seq shows that IpA is widespread in circulating immune cells, while multiple myeloma cells show loss of IpA isoforms that are normally expressed in plasma cells, impacting key genes in the disease.

    • Irtisha Singh
    • , Shih-Han Lee
    •  & Christina S. Leslie

  • Article
    | Open Access

    The integrity of the stratified epithelia relies on controlled cell turnover but it is unclear how mRNA binding proteins regulates this. Here, the authors show that the RNA binding protein Y-box binding protein-1 translationally represses cytokines, so preventing senescence and maintaining epidermal homeostasis.

    • Eunjeong Kwon
    • , Kristina Todorova
    •  & Anna Mandinova

  • Article
    | Open Access

    How transcription factors find their targets in vivo is still poorly understood. Here the authors use molecular dynamics simulations to investigate how transcription factors diffuse on chromatin, providing a theoretical framework for understanding the key role of genome conformation in this process.

    • Ruggero Cortini
    •  & Guillaume J. Filion

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