RNA metabolism articles within Nature Communications

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  • Article
    | Open Access

    Human APOBEC3H has several haplotypes and splice variants with distinct anti-HIV-1 activities, but the genetics underlying the expression of these variants are unclear. Here, the authors identify an intronic deletion in A3H haplotype II resulting in production of the most active splice variant, which is counteracted by HIV-1 protease.

    • Diako Ebrahimi
    • , Christopher M. Richards
    •  & Reuben S. Harris

  • Article
    | Open Access

    Incomplete splicing of HTT results in the production of the highly pathogenic exon 1 HTT protein. Here the authors identify the necessary intronic regions and the underlying mechanisms that contribute to this process.

    • Andreas Neueder
    • , Anaelle A. Dumas
    •  & Gillian P. Bates

  • Article
    | Open Access

    Mutations in mitochondrially-encoded tRNA genes can lead to mitochondrial disorders. Here the authors use next generation RNA sequencing to reveal the role of a N1 -methyladenosine modification in tRNALys MERR patients for translation elongation and the stability of selected nascent chains.

    • Uwe Richter
    • , Molly E. Evans
    •  & Brendan J. Battersby

  • Article
    | Open Access

    Roquin targets are known to contain two types of sequence-structure motifs, the constitutive and the alternative decay elements (CDE and ADE). Here, the authors describe a linear Roquin binding element (LBE) also involved in target recognition, and show that Roquin binding affects the translation of a subset of targeted mRNAs.

    • Katharina Essig
    • , Nina Kronbeck
    •  & Vigo Heissmeyer

  • Article
    | Open Access

    Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine repeats in the ATXN2 protein. Here the authors demonstrate that Staufen1, known to be an RNA-binding protein, interacts with ATXN2 and contributes to pathology in a mouse model of SCA2.

    • Sharan Paul
    • , Warunee Dansithong
    •  & Stefan M. Pulst

  • Article
    | Open Access

    The co-transcriptional capping of transcripts synthesized by RNA Pol II is substantially more efficient than capping of free RNA, a process that has been shown to depend on CTD phosphorylation. Here the authors demonstrate that a CTD-independent mechanism functions in parallel with CTD-dependent processes to ensure efficient capping.

    • Melvin Noe Gonzalez
    • , Shigeo Sato
    •  & Ronald C. Conaway

  • Article
    | Open Access

    Cytoplasmic PTEN is a tumor suppressor that antagonises PI3K signalling. Here, the authors show that nuclear PTEN can interact with the spliceosomal proteins and drive pre-mRNA splicing in a phosphatase-independent manner, in particular, PTEN depletion promotes Golgi extension and secretion through GOLGA2 exon skipping.

    • Shao-Ming Shen
    • , Yan Ji
    •  & Guo-Qiang Chen

  • 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

    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 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

    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

    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

    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

    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

    Arsenic resistance protein 2 (ARS2) plays an important role in nuclear RNA metabolism and interacts with the nuclear cap-binding complex (CBC). Here the authors present the human ARS2 structure and identify regions important for its interactions with binding partners supporting that mutually exclusive higher order CBC-ARS2 complexes are formed.

    • Wiebke Manuela Schulze
    • , Frank Stein
    •  & Stephen Cusack

  • Article
    | Open Access

    The nuclear pore complex is crucial for mediating nucleocytoplasmic exchanges. Here the authors use budding yeast to reveal a mechanism responsible of maintaining nucleoporin homeostasis by sensing changes in the complex integrity and further altering the metabolism of the corresponding mRNAs.

    • Jérôme O. Rouvière
    • , Manuel Bulfoni
    •  & Benoit Palancade

  • Article
    | Open Access

    Type I interferon signaling is critical for the control of infection. Here the authors show that zinc finger RNA-binding protein (ZFR) can control type I interferon responses, and that this control is itself regulated by distinct ZFR truncation patterns that differ between monocytes and macrophages.

    • Nazmul Haque
    • , Ryota Ouda
    •  & J. Robert Hogg

  • Article
    | Open Access

    The decapping enzyme Dcp2 removes the 5′ eukaryotic cap from mRNA transcripts and acts in concert with its essential activator Dcp1 and various coactivators. Here the authors present the structure of the fully-activated mRNA decapping complex, which reveals how Dcp2 recognizes the cap substrate and coactivators Edc1 and Edc3 activate catalysis.

    • Jeffrey S. Mugridge
    • , Ryan W. Tibble
    •  & John D. Gross

  • Article
    | Open Access

    UV-light-induced DNA damage affects RNA metabolism but the underlying signalling pathways are largely unexplored. Here, the authors show that UV light triggers p38-MK2-mediated phosphorylation of the NELF complex, promoting its release from chromatin and concurrent transcriptional elongation.

    • Marina E. Borisova
    • , Andrea Voigt
    •  & Petra Beli

  • Article
    | Open Access

    Mutations in BRCA1 are associated with an increased risk of breast and ovarian cancer. Here the authors show that EDC4, a component of P-bodies, is a member of the BRCA1 complex with roles in stimulating end resection at breaks.

    • Gonzalo Hernández
    • , María José Ramírez
    •  & Jordi Surrallés

  • Article
    | Open Access

    Methylated RNA bases influence many life processes, but current detection methods lack the ability to detect individual methylations in single cells. Here, the authors use fluorescence hybridization probes sensitive to methylation to detect specific epitranscriptomic modifications at the single-cell level.

    • Rohan T. Ranasinghe
    • , Martin R. Challand
    •  & David Klenerman

  • Article
    | Open Access

    UPF1 is a central protein in nonsense-mediated mRNA decay (NMD), but contribution of its RNA processivity to NMD is unclear. Here, the authors show how the retroviral Tax protein interacts with and inhibits UPF1, and demonstrate that UPF1’s translocase activity contributes to NMD.

    • Francesca Fiorini
    • , Jean-Philippe Robin
    •  & Vincent Mocquet

  • Article
    | Open Access

    While being known as a transcription factor, Kruppel-like factor 4 (Klf4) may have other molecular functions. This study shows that Klf4 in neural progenitor cells regulate neurogenesis and self-renewal by interacting with RNA-binding protein Staufen1 and RNA helicase Ddx5/17 to control mRNA decay.

    • Byoung-San Moon
    • , Jinlun Bai
    •  & Wange Lu

  • Article
    | Open Access

    The RNA-binding proteins Roquin-1 and Roquin-2 are essential for immune cell function and postnatal survival in mice. Here, the authors identify NUFIP2 as a cofactor of Roquin; Roquin binds and stabilizes NUFIP2 in cells while NUFIP2 regulates Roquin mRNA target recognition.

    • Nina Rehage
    • , Elena Davydova
    •  & Vigo Heissmeyer

  • Article
    | Open Access

    The mitochondrial RNA degradosome (mtEXO) plays an essential role in the regulation of mitochondrial gene expression and is composed of the 3′-to-5′ exoribonuclease Dss1 and the helicase Suv3. Here the authors present the RNA bound mtEXO crystal structure and give insights into its mechanism.

    • Michal Razew
    • , Zbigniew Warkocki
    •  & Marcin Nowotny

  • Article
    | Open Access

    The yeast and human RNA exosome is structurally related to prokaryotic phosphorylases but degrades RNA only via associated hydrolytic activities. Here the authors show that the RNA exosome of plants, and likely those of a few basal eukaryotes, combines phosphorolytic and hydrolytic activities to degrade RNA.

    • Natalia Sikorska
    • , Hélène Zuber
    •  & Dominique Gagliardi

  • Article
    | Open Access

    Several families of natural compounds target core components of the pre-mRNA splicing machinery and display anti-tumor activity. Here the authors show that particular sequence features can be linked to drug response, and that drugs with very similar chemical structures display substantially different effects on splicing regulation.

    • Luisa Vigevani
    • , André Gohr
    •  & Juan Valcárcel

  • Article
    | Open Access

    A nucleotide repeat expansion in C9orf72 is a common genetic cause of neurodegenerative disorders. Here, the authors provide insight into the molecular mechanism by which this repeat undergoes Repeat-Associated Non-AUG (RAN) translation, implicating the integrated stress response and eIF2α phosphorylation.

    • Katelyn M. Green
    • , M. Rebecca Glineburg
    •  & Peter K. Todd

  • Article
    | Open Access

    Little is known about the changes in mRNA splicing, processing and stability that can alter gene expression during heart failure. Here, the authors show that BEX1 is induced during heart failure and is part of a ribonucleoprotein complex enhancing the expression and stability of proinflammatory genes.

    • Federica Accornero
    • , Tobias G. Schips
    •  & Jeffery D. Molkentin

  • Article
    | Open Access

    Excision of internal transcribed spacer 2 (ITS2) within eukaryotic pre-ribosomal RNA is essential for ribosome function. Here, the authors reconstitute the entire cycle of ITS2 processing in vitro using purified components, providing insights into the cleavage process and demonstrating that 26S pre-rRNA processing necessarily precedes 7S pre-rRNA processing.

    • Lisa Fromm
    • , Sebastian Falk
    •  & Ed Hurt

  • Article
    | Open Access

    The mitochondrial genome, being compressed to 16 kb, is an attractive model system to investigate how RNA-binding proteins chaperone mRNA lifecycles. Here the authors use RNase footprinting and PAR-CLIP to show that the LRPPRC–SLIRP complex stabilizes mRNA structures to expose sites required for translation and polyadenylation.

    • Stefan J. Siira
    • , Henrik Spåhr
    •  & Aleksandra Filipovska

  • Article
    | Open Access

    Small molecules correcting the splicing deficit of the survival of motor neuron 2 (SMN2) gene have been identified as having therapeutic potential. Here, the authors provide evidence that SMN2 mRNA forms a ribonucleoprotein complex that can be specifically targeted by these small molecules.

    • Manaswini Sivaramakrishnan
    • , Kathleen D. McCarthy
    •  & Friedrich Metzger

  • Article
    | Open Access

    Unlike transcriptional regulation of hESC identity, little is known post-transcriptionally. Here, the authors show that the RNA binding protein CSDE1 regulates core components of hESC identity, neurectoderm commitment and neurogenesis to maintain pluripotency and prevent neural differentiation.

    • Hyun Ju Lee
    • , Deniz Bartsch
    •  & David Vilchez

  • Article
    | Open Access

    The nuclear cap-binding complex (CBC) binds to the 5′-cap structure of Pol II transcripts. Here, the authors give structural insights into CBC-mediated transcript processing and show that CBC forms mutual exclusive complexes with NELF and ARS2, which might act in earlier and later phases of transcription, respectively.

    • Wiebke Manuela Schulze
    •  & Stephen Cusack

  • Article
    | Open Access

    Adenomatous polyposis coli (APC) regulates the localization of some mRNAs at cellular protrusions but the underlying mechanisms and functional roles are not known. Here the authors show that APC-dependent RNAs are enriched in contractile protrusions, via detyrosinated microtubules, and enhance cell migration.

    • Tianhong Wang
    • , Susan Hamilla
    •  & Stavroula Mili

  • Article
    | Open Access

    Ribosome biogenesis is a dynamic process that involves the ordered assembly of ribosomal proteins and numerous RNA structural rearrangements. Here the authors apply ChemModSeq, a high-throughput RNA structure probing method, to quantitatively measure changes in RNA flexibility during the nucleolar stages of 60S assembly in yeast.

    • Elena Burlacu
    • , Fredrik Lackmann
    •  & Sander Granneman

  • Article
    | Open Access

    FAM46C is one of the most frequently mutated genes in multiple myeloma (MM), but its molecular function remains unknown. Here the authors show that FAM46C is a poly(A) polymerase and that loss of function of FAM46C drives multiple myeloma through the destabilisation of ER response transcripts.

    • Seweryn Mroczek
    • , Justyna Chlebowska
    •  & Andrzej Dziembowski

  • Article
    | Open Access

    Subcellular localization of RNAs and proteins is important for polarized cells such as neurons. Here the authors differentiate mouse embryonic stem cells into neurons, and analyze the local transcriptome, proteome, and translated transcriptome in their cell bodies and neurites, providing a unique resource for future studies on neuronal polarity.

    • Alessandra Zappulo
    • , David van den Bruck
    •  & Marina Chekulaeva

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