RNA metabolism articles within Nature Communications

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  • Article
    | Open Access

    Synthetic circuits in host cells compete with endogenous processes for limited resources. Here the authors use MazF to funnel cellular resources to a synthetic circuit to increase product production and demonstrate how resource allocation can be manipulated.

    • Ophelia S. Venturelli
    • , Mika Tei
    •  & Adam P Arkin

  • Article
    | Open Access

    The RNA binding protein FUS functions in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Here the authors show that FUS controls back-splicing reactions leading to circular RNA (circRNA) production in stem cell-derived motor neurons and that ALS-associated FUS mutations affect the biogenesis of circRNAs.

    • Lorenzo Errichelli
    • , Stefano Dini Modigliani
    •  & Irene Bozzoni

  • Article
    | Open Access

    The decline of DNA and protein quality control contributes to organismal ageing. Here, Sonet al. report that nonsense-mediated mRNA decay, a RNA quality control mechanism, is enhanced in long-lived daf-2 mutant worms and contributes to their longevity by regulating expression of the yars-2/tyrosyl tRNA synthetase.

    • Heehwa G. Son
    • , Mihwa Seo
    •  & Seung-Jae V. Lee

  • Article
    | Open Access

    The phosphorylation of serine/arginine-rich proteins by CDC-like kinase is a central regulatory mechanism for RNA splicing reactions. Here, the authors synthesize a novel small molecule CLK inhibitor and map CLK-responsive alternative splicing events and discover an effect on conjoined gene transcription.

    • Tyler Funnell
    • , Shinya Tasaki
    •  & Samuel Aparicio

  • Article
    | Open Access

    Nonsense-mediated mRNA decay (NMD) is a quality control pathway that recognizes and degrades transcripts harbouring nonsense mutations. Here the authors show that the ATPase activity of UPF1 mediates functional interactions between the NMD machinery and ribosomes required for efficient ribosome release at premature termination codons.

    • Lucas D. Serdar
    • , DaJuan L. Whiteside
    •  & Kristian E. Baker

  • Article
    | Open Access

    mRNA surveillance is essential to maintain homeostasis in eukaryotes and is activated by mRNAs lacking a stop codon. Here the authors describe a high resolution cryo-EM structure of a nonstop complex that shows how arrested ribosome recognition is achieved during Dom34-mediated mRNA surveillance.

    • Tarek Hilal
    • , Hiroshi Yamamoto
    •  & Christian M.T. Spahn

  • Article
    | Open Access

    Degradation of messenger RNA is a key regulatory step in controlling eukaryotic gene expression. Here the authors present xrFrag, a molecular tool to interrogate the extent and directionality of mRNA turnover by the detection of stabilized decay intermediates produced by several common decay pathways.

    • Volker Boehm
    • , Jennifer V. Gerbracht
    •  & Niels H. Gehring

  • Article
    | Open Access

    RBM7 and ZCCHC8 are two core subunits of the Nuclear Exosome Targeting complex, which regulates the degradation of selected non-coding RNAs in human cells. Here, the authors use structural and biochemical methods to show how ZCCHC8 recruits RBM7 in the complex, leaving the RNA binding site accessible and revealing possible implications for splicing.

    • Sebastian Falk
    • , Ksenia Finogenova
    •  & Elena Conti

  • Article
    | Open Access

    The chromatin-associated protein AKAP95 is known for its chromatin-related functions including enhancing transcription. Here the authors show that AKAP95 interacts with the splicing regulatory factors as well as RNAs to regulate the inclusion of exons and pre-mRNA splicing.

    • Jing Hu
    • , Alireza Khodadadi-Jamayran
    •  & Hao Jiang

  • Article
    | Open Access

    Gene expression is regulated by a range of mechanisms, including post-translational modifications such as phosphorylation. Here the authors present evidence for a feedback mechanism whereby hyperphosphorylation of UPF1 in response to delays in nonsense-mediated decay enhances recruitment of mRNA decay machinery.

    • Sébastien Durand
    • , Tobias M. Franks
    •  & Jens Lykke-Andersen

  • Article
    | Open Access

    The transport of secretory proteins from the endoplasmic reticulum to the Golgi depends on COPII-coated vesicles. Here, the authors show that activation-induced alternative splicing of Sec16 controls adaptation of COPII transport to increased secretory cargo upon T cell activation.

    • Ilka Wilhelmi
    • , Regina Kanski
    •  & Florian Heyd

  • Article
    | Open Access

    RNA editing rate detected from bulk RNA-seq data can vary widely. Here, by constructing a hierarchical Bayesian model, the authors report substantial variance in editing signatures detected by RNA-seq data from both single cells and a cognate bulk sample.

    • Dewi Harjanto
    • , Theodore Papamarkou
    •  & Anastasia Papavasiliou

  • Article
    | Open Access

    Alternative splicing and alternative polyadenylation (APA) contribute to mRNA diversity but are difficult to assess using short read RNA-seq data. Here, the authors use single molecule long-read isoform sequencing and develop a computational pipeline to identify full-length splice isoforms and APA sites in sorghum.

    • Salah E. Abdel-Ghany
    • , Michael Hamilton
    •  & Anireddy S. N. Reddy

  • Article
    | Open Access

    Genotype–phenotype landscapes are an important characteristic for understanding the evolution of traits. Here the authors construct the local landscape for the alternative splicing of FAS/CD95 exon 6, revealing the regulation of splicing and the evolution of regulatory information between species.

    • Philippe Julien
    • , Belén Miñana
    •  & Ben Lehner

  • Article
    | Open Access

    MALT1 regulates NFκB signalling both as a scaffolding protein and as a protease. Here the authors show that during T cell activation the expression of MALT1 gene switches to an alternatively spliced variant, which increases TCR signal transduction due to enhanced TRAF6 binding.

    • Isabel Meininger
    • , Richard A. Griesbach
    •  & Daniel Krappmann

  • Article
    | Open Access

    Patients with myotonic dystrophy (MD) suffer from severe cardiac issues of unknown aetiology. Freyermuth et al. show that fatal changes in cardiac electrophysiological properties in humans and mice with MD may arise from misregulation of the alternative splicing of the cardiac Na+ channel SCN5Atranscript, resulting in expression of its fetal form.

    • Fernande Freyermuth
    • , Frédérique Rau
    •  & Nicolas Charlet-Berguerand

  • Article
    | Open Access

    Post-transcriptional control of RNA is important in health and disease. Here, the authors show that the RNA-binding protein Quaking guides pre-mRNA splicing and transcript abundance during monocyte to macrophage differentiation, and that Quaking depletion impairs pro-atherogenic foam cell formation.

    • Ruben G. de Bruin
    • , Lily Shiue
    •  & Eric P. van der Veer

  • Article
    | Open Access

    Nuclear bodies can nucleate at sites of active transcription and are beneficial for efficient gene expression. Here, the authors show that Cajal bodies, a prominent type of nuclear body, contribute to genome organization with global effects on gene expression and RNA splicing fidelity.

    • Qiuyan Wang
    • , Iain A. Sawyer
    •  & Miroslav Dundr

  • Article
    | Open Access

    UPF1 is a central Nonsense-mediated mRNA decay—(NMD), a mechanism to degrade mRNAs containing premature translation termination codons-factor—whose phosphorylation is key to triggering NMD. Here the authors show that the DHX34 helicase acts as a scaffold in promoting UPF1 phosphorylation by SMG1 to promotes NMD.

    • Roberto Melero
    • , Nele Hug
    •  & Oscar Llorca

  • Article
    | Open Access

    Activation-induced deoxycytidine deaminase (AID) induces somatic hypermutation and class-switch recombination during transcription of immunoglobulin genes. Here the authors use single-molecule FRET to show that AID translocates together with RNA polymerase and scans within stalled transcription bubbles.

    • Gayan Senavirathne
    • , Jeffrey G. Bertram
    •  & David Rueda

  • Article
    | Open Access

    Alternative RNA splicing is important during organismal development. Here, the authors perform RNA-Seq on mouse and human liver samples to provide a comprehensive view of splicing events during liver development and growth, and identify Espr2 as a main regulator of these splicing processes.

    • Amruta Bhate
    • , Darren J. Parker
    •  & Auinash Kalsotra

  • Article
    | Open Access

    Roifman Syndrome is a rare disorder whose disease manifestations include growth retardation, spondyloepiphyseal dysplasia and immunodeficiency. Here, the authors use whole-genome sequencing to discover that rare compound heterozygous variants disrupting the small nuclear RNA gene RNU4ATACcause Roifman Syndrome.

    • Daniele Merico
    • , Maian Roifman
    •  & Stephen W. Scherer

  • Article
    | Open Access

    mRNA deadenylation, the first step in regulated degradation, is mediated by the action of the CCR4-NOT and PAN2-PAN3 complexes. Here the authors show that the RNA-binding E3 ubiquitin-ligase MEX-3C associates with the CCR4-NOT complex and ubiquitinates the catalytic subunit CNOT7 to regulate its deadenylation activity.

    • Florencia Cano
    • , Radu Rapiteanu
    •  & Paul J. Lehner

  • Article
    | Open Access

    The alternative splicing factor Nova2 is best known for its pivotal function in the brain. Giampietro et al. reveal an important role for Nova2 in the regulation of alternative splicing of transcripts in the vascular endothelium that are crucial for the maintenance of endothelial cell polarity and vessel lumen formation in zebrafish.

    • Costanza Giampietro
    • , Gianluca Deflorian
    •  & Claudia Ghigna

  • Article
    | Open Access

    The processing of RNAs transcribed by RNA polymerase II requires a cap-binding complex (CBC), consisting of NCBP1 and NCBP2. Here, the authors report an alternative CBC formed by NCBP1 and a previously uncharacterized protein, NCBP3 that is critical for RNA processing under cellular stress conditions.

    • Anna Gebhardt
    • , Matthias Habjan
    •  & Andreas Pichlmair

  • Article
    | Open Access

    Adenosine-to-inosine (A-to-I) RNA editing plays an important role in neurological functions. Here, by a quantitative trait loci (QTL) mapping approach in 131 Drosophila melanogasterstrains, the authors identify 545 QTLs associated with differences in RNA editing.

    • Gokul Ramaswami
    • , Patricia Deng
    •  & Jin Billy Li

  • Article
    | Open Access

    Upf1 is a multifunctional helicase involved in various DNA- and RNA-related processes, including nonsense-mediated mRNA decay (NMD). Here the authors demonstrate that Upf1 is a highly processive ribonucleoprotein complex remodeler—a capability likely important for Upf1’s NMD function.

    • Francesca Fiorini
    • , Debjani Bagchi
    •  & Vincent Croquette

  • Article
    | Open Access

    Eukaryotic ribosomal proteins contain nuclear localization signals (NLSs) that their bacterial counterparts lack. Here the authors compare homologous proteins from bacterial and eukaryotic ribosomes to show how NLSs could emerge in the course of evolution, and use this knowledge to identify novel NLSs.

    • Sergey Melnikov
    • , Adam Ben-Shem
    •  & Marat Yusupov

  • Article
    | Open Access

    Herpes simplex virus 1 (HSV-1) efficiently shuts down host gene expression in infected cells. Here Rutkowski et al. analyse the genome-wide changes in transcription and translation in infected cells, and show that HSV-1 triggers an extensive disruption of transcription termination of cellular genes.

    • Andrzej J. Rutkowski
    • , Florian Erhard
    •  & Lars Dölken

  • Article |

    BRAF inhibitors have shown encouraging clinical effects in melanoma patients; however, patients rapidly develop resistance via different mechanisms including alternative splicing. Here the authors find a specific mutation affecting BRAF splicing and highlight the therapeutic potential of splicing interference.

    • Maayan Salton
    • , Wojciech K. Kasprzak
    •  & Tom Misteli

  • Article
    | Open Access

    Aberrant RNA editing is linked to a range of neuropsychiatric and chronic diseases. Here Sharma et al. show that APOBEC3A can function as an RNA editing protein in response to physiological stimuli, significantly expanding our understanding of RNA editing and the role this may play in diseases.

    • Shraddha Sharma
    • , Santosh K. Patnaik
    •  & Bora E. Baysal

  • Article |

    Nonsense-mediated mRNA decay (NMD) is a pathway that controls endogenous transcript levels and limits the production of aberrant mRNAs. Here the authors show that NMD is attenuated in cells treated with chemotherapeutic compounds through caspase-mediated proteolytic cleavage of UPF1, a key NMD effector.

    • Maximilian W. Popp
    •  & Lynne E. Maquat

  • Article |

    ADAR1 is an adenosine deaminase that converts adenosine to inosine (A-to-I) mostly on Alu repeats in human RNA. Here by analysing transcriptome-wide ADAR1–RNA interactions, the authors show that ADAR1 also binds non-Alusequences to regulate alternative 3′ UTR usage and miRNA biogenesis in the nucleus.

    • Jae Hoon Bahn
    • , Jaegyoon Ahn
    •  & Xinshu Xiao

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