RNA metabolism

  • Article
    | Open Access

    Maintenance of high turnover in tissues such as epidermis requires balance between proliferation and differentiation. Here the authors show that HNRNPK promotes RNA Polymerase II binding to proliferation and self-renewal genes as well as degradation of differentiation promoting mRNAs together with DDX6 in epidermis.

    • Jingting Li
    • , Yifang Chen
    •  & George L. Sen
  • Article
    | Open Access

    We currently lack generic methods to map RNA modifications across the entire transcriptome. Here, the authors demonstrate that m6A RNA modifications can be detected with high accuracy using nanopore direct RNA sequencing.

    • Huanle Liu
    • , Oguzhan Begik
    •  & Eva Maria Novoa
  • Article
    | Open Access

    The biosynthesis of N6-threonylcarbamoylated adenosine 37 in tRNA (t6A) involves the YRDC enzyme and the KEOPS complex. Here, the authors report mutations in YRDC and the KEOPS component GON7 in Galloway-Mowat syndrome and determine the crystal structure of a GON7-containg subcomplex that suggests a role in KEOPS complex stability.

    • Christelle Arrondel
    • , Sophia Missoury
    •  & Géraldine Mollet
  • Article
    | Open Access

    Cytosolic RNA degradation by the RNA exosome requires the Ski complex. Here the authors show that the proteins RST1 and RIPR assist the RNA exosome and the Ski complex in RNA degradation, thereby preventing the production of secondary siRNAs from endogenous mRNAs.

    • Heike Lange
    • , Simon Y. A. Ndecky
    •  & Dominique Gagliardi
  • Article
    | Open Access

    Ime4p is a yeast N6-methyladenosine (m6A) methyltransferase with an unknown role in meiosis. Rme1p is a repressor of meiosis. Here the authors show that Ime4p methylates RME1 3′ UTR to reduce its expression and enable meiosis, thus providing an example of an m6A site with a physiological role.

    • G. Guy Bushkin
    • , David Pincus
    •  & Gerald R. Fink
  • Article
    | Open Access

    Transfer RNA (tRNA) is regulated by RNA modifications. Here the authors employ time-resolved NMR to monitor modifications of yeast tRNAPhe in cellular extracts, revealing a sequential order and cross-talk between modifications.

    • Pierre Barraud
    • , Alexandre Gato
    •  & Carine Tisné
  • Article
    | Open Access

    Asymmetric subcellular mRNA distribution is important for local translation of neuronal mRNAs. Here the authors employed MS2 live-cell imaging and showed that the reporter mRNA containing the 3’ UTR of Rgs4 shows an anterograde transport bias, dependent on neuronal activity and the protein Staufen2, and mediates sustained mRNA recruitment to synapses.

    • Karl E. Bauer
    • , Inmaculada Segura
    •  & Michael A. Kiebler
  • Article
    | Open Access

    DEAD-box helicases (DDXs) function in an ATP-dependent, non-processive manner and the conserved helicase core is composed of two RecA-like domains D1 and D2. Here the authors present the crystal structure of the D1D2 core from human DDX3X bound to a 23-base pair dsRNA in the pre-unwound state and discuss the implications for helicase mechanism.

    • He Song
    •  & Xinhua Ji
  • Article
    | Open Access

    5-carboxymethoxyuridine (cmo5U) is one of the RNA modifications found in bacterial tRNA anticodons. Here the authors show that the first step of cmo5U biosynthesis from uridine is mediated by either one of two parallel factors, TrhP or TrhO, and that cmo5U modification is required for efficient translation.

    • Yusuke Sakai
    • , Satoshi Kimura
    •  & Tsutomu Suzuki
  • Article
    | Open Access

    Multidomain RNA-binding proteins recognize specific target sequences through mechanisms that are not well understood. Here the authors present an integrated approach to define the RNA-binding specificity and RNP topology and apply it to the analysis of the prototypical multidomain RNA-binding protein IMP3.

    • Tim Schneider
    • , Lee-Hsueh Hung
    •  & Albrecht Bindereif
  • Article
    | Open Access

    Several lncRNAs are regulated by TGF-β. Here the authors report that an intergenic lncRNA —EPR— is a component of the TGF-β signaling pathway and controls epithelial cell proliferation by altering transcription and mRNA decay of Cdkn1a. EPR overexpression restrains tumor growth of orthotopically transplanted mice.

    • Martina Rossi
    • , Gabriele Bucci
    •  & Roberto Gherzi
  • Article
    | Open Access

    Terminal uridylyltransferase 4/7 (TUT4/7) binds to Lin28 and modifies let-7 precursor (pre-let-7) to regulate cell differentiation and proliferation. Here the authors report the crystal structure of the N-terminal Lin28-interacting module of TUT4, showing a role of the N-terminal zinc finger domain in stabilizing the Lin28:pre-let-7:TUT4 ternary complex.

    • Seisuke Yamashita
    • , Takashi Nagaike
    •  & Kozo Tomita
  • Article
    | Open Access

    Bumblebee workers are genetically highly similar but they show different behaviors such as brood care and foraging. Here the authors report a high level of ADAR-mediated RNA editing in the bumblebee Bombus terrestris and its weak correlation to task performance.

    • Hagit T. Porath
    • , Esther Hazan
    •  & Guy Bloch
  • Article
    | Open Access

    CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors investigate the function an alternatively spliced shorter CTCF isoform, finding that this isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.

    • Jiao Li
    • , Kaimeng Huang
    •  & Hongjie Yao
  • Article
    | Open Access

    Polyadenylation stabilizes edited mitochondrial mRNAs in Trypanosoma brucei, but the involved poly(A) binding protein is unknown. Here, Mesitov et al. show that a pentatricopeptide repeat factor KPAF4 binds to A-tail and prevents exonucleolytic degradation as well as translation of incompletely edited mRNAs.

    • Mikhail V. Mesitov
    • , Tian Yu
    •  & Inna Aphasizheva
  • Article
    | Open Access

    Splicing factors are often mutated in hematological malignancies. Here, the authors perform an in vivo shRNA screen in a CEBPA mutant AML mouse model and identify that RBM25 controls the splicing of pre-mRNAs encoding BCL-X and BIN1 to exert its tumour suppressor activities in AML.

    • Ying Ge
    • , Mikkel Bruhn Schuster
    •  & Bo Torben Porse
  • Article
    | Open Access

    Pre-ribosomes undergo numerous structural rearrangements during their assembly. Here the authors identify the binding sites of three essential RNA helicases on pre-ribosomal particles, enabling them to provide insights into the structural and compositional changes that occur during biogenesis of the large ribosomal subunit.

    • Lukas Brüning
    • , Philipp Hackert
    •  & Markus T. Bohnsack
  • Article
    | Open Access

    Myotonic dystrophy type 1 (DM1) is associated with aberrant transcript splicing. Here, the authors develop a transgenic mouse model expressing a bi-chromatic reporter system that allows non-invasive monitoring of splicing of a transcript altered in DM1 in vivo, and show that it allows for evaluation of the therapeutic response to treatment with antisense oligonucleotides.

    • Ningyan Hu
    • , Layal Antoury
    •  & Thurman M. Wheeler
  • Article
    | Open Access

    Termination of RNA polymerase II (RNAPII) transcription is an essential step of gene expression. Here the authors provide evidence that in fission yeast termination of ncRNA genes occurs by a cleavage-dependent mechanism involving recruitment of mRNA 3′ end processing factors and requires the conserved Ysh1/CPSF-73 and Dhp1/XRN2 nucleases.

    • Marc Larochelle
    • , Marc-Antoine Robert
    •  & François Bachand
  • Article
    | Open Access

    T-acute lymphoblastic leukemia is an aggressive cancer. Here the authors provide insights into the functional role of SHQ1, an H/ACA snoRNP assembly factor involved in snRNA pseudouridylation, in T-lymphoblastic leukemia cell survival through regulating the maturation of MYC mRNA.

    • Hexiu Su
    • , Juncheng Hu
    •  & Hudan Liu
  • 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