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Table of Contents

April 2022 | Volume 5, No. 4

Research Articles

  • Mammalian splicing divergence is shaped by drift, buffering in <em>trans</em>, and a scaling law
    Open Access
    Mammalian splicing divergence is shaped by drift, buffering in trans, and a scaling law

    Xudong Zou, Bernhard Schaefke, Yisheng Li, Fujian Jia, Wei Sun, Guipeng Li, Weizheng Liang, Tristan Reif, Florian Heyd, Qingsong Gao, Shuye Tian, Yanping Li, Yisen Tang, Liang Fang, Yuhui Hu, Wei Chen

    Xudong Zou ... Wei Chen

    Published 30 December 2021

    This study globally investigates the allelic splicing pattern in multiple tissues of an F1 hybrid mouse and reveals the underlying driving forces shaping such tissue-dependent splicing divergence.

  • Retinoblastoma protein regulates carcinogen susceptibility at heterochromatic cancer driver loci
    Open Access
    Retinoblastoma protein regulates carcinogen susceptibility at heterochromatic cancer driver loci

    Ka Man Wong, Devin A King, Erin K Schwartz, Rafael E Herrera, Ashby J Morrison

    Ka Man Wong ... Ashby J Morrison

    Published 4 January 2022

    The retinoblastoma protein regulates mutagenic potential via control of UV-induced DNA lesion acquisition, thus revealing novel mechanisms that contribute to its tumor suppressor capabilities.

  • New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain
    Open Access
    New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain

    Ralph T Böttcher, Nico Strohmeyer, Jonas Aretz, Reinhard Fässler

    Ralph T Böttcher ... Reinhard Fässler

    Published 7 January 2022

    This study investigates phosphorylation of and kindlin recruitment by the double-threonine motif in the β1 integrin cytoplasmic tails.

  • Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in <em>Drosophila</em> muscles
    Open Access
    Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles

    Elena Nikonova, Amartya Mukherjee, Ketaki Kamble, Christiane Barz, Upendra Nongthomba, Maria L Spletter

    Elena Nikonova ... Maria L Spletter

    Published 7 January 2022

    Rbfox1 is required for the development of both fibrillar and tubular muscle fibers in adult Drosophila and interacts with Bruno1 to define fiber type–specific patterns of alternative splicing.

  • Cap analysis of gene expression reveals alternative promoter usage in a rat model of hypertension
    Open Access
    Cap analysis of gene expression reveals alternative promoter usage in a rat model of hypertension

    Sonal Dahale, Jorge Ruiz-Orera, Jan Silhavy, Norbert Hübner, Sebastiaan van Heesch, Michal Pravenec, Santosh S Atanur

    Sonal Dahale ... Santosh S Atanur

    Published 7 January 2022

    Cap analysis of gene expression (CAGE) tag sequencing from left ventricles of a rat model of hypertension identifies genes that use alternative promoters in a disease condition.

  • Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH
    Open Access
    Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH

    Elena Rensen, Stefano Pietropaoli, Florian Mueller, Christian Weber, Sylvie Souquere, Sina Sommer, Pierre Isnard, Marion Rabant, Jean-Baptiste Gibier, Fabiola Terzi, Etienne Simon-Loriere, Marie-Anne Rameix-Welti, Gérard Pierron, Giovanna Barba-Spaeth, Christophe Zimmer

    Elena Rensen ... Christophe Zimmer

    Published 7 January 2022

    We design an RNA-FISH method to target the plus and minus strands of SARS-CoV-2 RNA, and apply it to image the virus in cell lines, lung tissue, and nasal swabs, by fluorescence and electron microscopy.

  • Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19
    Open Access
    Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

    Jose F Varona, Pedro Landete, Jose A Lopez-Martin, Vicente Estrada, Roger Paredes, Pablo Guisado-Vasco, Lucia Fernandez de Orueta, Miguel Torralba, Jesus Fortun, Roberto Vates, Jose Barberan, Bonaventura Clotet, Julio Ancochea, Daniel Carnevali, Noemi Cabello, Lourdes Porras, Paloma Gijon, Alfonso Monereo, Daniel Abad, Sonia Zuñiga, Isabel Sola, Jordi Rodon, Julia Vergara-Alert, Nuria Izquierdo-Useros, Salvador Fudio, Maria Jose Pontes, Beatriz de Rivas, Patricia Giron de Velasco, Antonio Nieto, Javier Gomez, Pablo Aviles, Rubin Lubomirov, Alvaro Belgrano, Belen Sopesen, Kris M White, Romel Rosales, Soner Yildiz, Ann-Kathrin Reuschl, Lucy G Thorne, Clare Jolly, Greg J Towers, Lorena Zuliani-Alvarez, Mehdi Bouhaddou, Kirsten Obernier, Briana L McGovern, M Luis Rodriguez, Luis Enjuanes, Jose M Fernandez-Sousa, Nevan J Krogan, Jose M Jimeno, Adolfo Garcia-Sastre

    Jose F Varona ... Adolfo Garcia-Sastre

    Published 10 January 2022

    This proof-of-concept study shows that plitidepsin, a marine peptide that inhibits SARS-CoV-2 replication, has a favorable safety profile and may be an efficacious treatment for patients with COVID-19.

  • Chl1 helicase controls replication fork progression by regulating dNTP pools
    Open Access
    Chl1 helicase controls replication fork progression by regulating dNTP pools

    Amandine Batté, Sophie C van der Horst, Mireille Tittel-Elmer, Su Ming Sun, Sushma Sharma, Jolanda van Leeuwen, Andrei Chabes, Haico van Attikum

    Amandine Batté ... Haico van Attikum

    Published 11 January 2022

    Chl1 helicase affects RPA-dependent checkpoint activation after replication fork arrest by ensuring proper dNTP levels, thereby controlling replication fork progression under stress conditions.

  • Identification of human gene research articles with wrongly identified nucleotide sequences
    Open Access
    Identification of human gene research articles with wrongly identified nucleotide sequences

    Yasunori Park, Rachael A West, Pranujan Pathmendra, Bertrand Favier, Thomas Stoeger, Amanda Capes-Davis, Guillaume Cabanac, Cyril Labbé, Jennifer A Byrne

    Yasunori Park ... Jennifer A Byrne

    Published 12 January 2022

    This study describes Seek & Blastn analysis of targeted and journal corpora with manual results verification to identify human gene research articles with wrongly identified nucleotide sequence reagents.

  • Structural basis of Nrd1–Nab3 heterodimerization
    Open Access
    Structural basis of Nrd1–Nab3 heterodimerization

    Belén Chaves-Arquero, Santiago Martínez-Lumbreras, Sergio Camero, Clara M Santiveri, Yasmina Mirassou, Ramón Campos-Olivas, Maria Ángeles Jiménez, Olga Calvo, José Manuel Pérez-Cañadillas

    Belén Chaves-Arquero ... José Manuel Pérez-Cañadillas

    Published 12 January 2022

    The NMR structure of an Nrd1–Nab3 chimera describes the structural bases of Nrd1/Nab3 heterodimerization. Nrd1 embraces a bundle of helices in Nab3, building a large interface. Key mutations at that interface compromise cell fitness.

  • Sumoylation of Cas9 at lysine 848 regulates protein stability and DNA binding
    Open Access
    Sumoylation of Cas9 at lysine 848 regulates protein stability and DNA binding

    Tunahan Ergünay, Özgecan Ayhan, Arda B Celen, Panagiota Georgiadou, Emre Pekbilir, Yusuf T Abaci, Duygu Yesildag, Mandy Rettel, Ulduz Sobhiafshar, Anna Ogmen, NC Tolga Emre, Umut Sahin

    Tunahan Ergünay ... Umut Sahin

    Published 12 January 2022

    Cas9 is sumoylated and ubiquitylated in human cells. K848 is the major SUMO2/3 modification site, but multiple lysines are ubiquitylated, precipitating proteasomal degradation. Preventing Cas9 sumoylation by K848 ablation or by pharmacologic means reduces Cas9 half-life and DNA binding ability.

  • Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model
    Open Access
    Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model

    Megumi Akamatsu, Takenari Yamashita, Sayaka Teramoto, Zhen Huang, Janet Lynch, Tatsushi Toda, Li Niu, Shin Kwak

    Megumi Akamatsu ... Shin Kwak

    Published 12 January 2022

    RNA aptamers designed to block AMPA receptors effectively reduce progression of motor dysfunction, improve TDP-43 pathology, and prevent death of motor neurons in AR2 mice, a mouse model of sporadic ALS, without adverse effects.

  • Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF
    Open Access
    Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF

    Stefanie Dichtl, David E Sanin, Carolin K Koss, Sebastian Willenborg, Andreas Petzold, Maria C Tanzer, Andreas Dahl, Agnieszka M Kabat, Laura Lindenthal, Leonie Zeitler, Sabrina Satzinger, Alexander Strasser, Matthias Mann, Axel Roers, Sabine A Eming, Karim C El Kasmi, Edward J Pearce, Peter J Murray

    Stefanie Dichtl ... Peter J Murray

    Published 13 January 2022

    Pro-inflammatory TNF is a highly gene-selective inhibitor of the gene expression program of tissue repair and wound healing macrophages.

  • Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques
    Open Access
    Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques

    Emily Speranza, Jyothi N Purushotham, Julia R Port, Benjamin Schwarz, Meaghan Flagg, Brandi N Williamson, Friederike Feldmann, Manmeet Singh, Lizzette Pérez-Pérez, Gail L Sturdevant, Lydia M Roberts, Aaron Carmody, Jonathan E Schulz, Neeltje van Doremalen, Atsushi Okumura, Jamie Lovaglio, Patrick W Hanley, Carl Shaia, Ronald N Germain, Sonja M Best, Vincent J Munster, Catharine M Bosio, Emmie de Wit

    Emily Speranza ... Emmie de Wit

    Published 17 January 2022

    Increased age is a risk factor for severe COVID-19. Multi-omics profiling in rhesus macaques suggests that aging may delay or impair cellular immune responses and the return to immune homeostasis.

  • Malaria abrogates O’nyong–nyong virus pathologies by restricting virus infection in nonimmune cells
    Open Access
    Malaria abrogates O’nyong–nyong virus pathologies by restricting virus infection in nonimmune cells

    Anthony Torres-Ruesta, Teck-Hui Teo, Yi-Hao Chan, Siti Naqiah Amrun, Nicholas Kim-Wah Yeo, Cheryl Yi-Pin Lee, Samantha Yee-Teng Nguee, Matthew Zirui Tay, Francois Nosten, Siew-Wai Fong, Fok-Moon Lum, Guillaume Carissimo, Laurent Renia, Lisa FP Ng

    Anthony Torres-Ruesta ... Lisa FP Ng

    Published 17 January 2022

    This study reveals that acute blood-stage malaria promotes resistance to ONNV infection by inducing IFNg-dependent antiviral status in human and murine nonimmune cells.

  • Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells
    Open Access
    Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells

    Johanna Grinat, Frauke Kosel, Neha Goveas, Andrea Kranz, Dimitra Alexopoulou, Klaus Rajewsky, Michael Sigal, A Francis Stewart, Julian Heuberger

    Johanna Grinat ... Julian Heuberger

    Published 21 January 2022

    The histone methyltransferase Mll1 controls intestinal secretory cell fate by promoting Wnt-driven Paneth and restricting Mapk-dependent goblet cell differentiation through regulation of Gata4/6 transcription factors

  • Phenylbutyrate rescues the transport defect of the Sec61α mutations V67G and T185A for renin
    Open Access
    Phenylbutyrate rescues the transport defect of the Sec61α mutations V67G and T185A for renin

    Mark Sicking, Martina Živná, Pratiti Bhadra, Veronika Barešová, Andrea Tirincsi, Drazena Hadzibeganovic, Kateřina Hodaňová, Petr Vyleťal, Jana Sovová, Ivana Jedličková, Martin Jung, Thomas Bell, Volkhard Helms, Anthony J Bleyer, Stanislav Kmoch, Adolfo Cavalié, Sven Lang

    Mark Sicking ... Sven Lang

    Published 21 January 2022

    Using cellular models of the ADTKD–SEC61A1 causing mutations V67G and T185A, this study reveals specific aberrations of protein transport and calcium homeostasis as a potential pathogenic mechanism.

  • Nucleotide biosynthesis links glutathione metabolism to ferroptosis sensitivity
    Open Access
    Nucleotide biosynthesis links glutathione metabolism to ferroptosis sensitivity

    Amy Tarangelo, Jason Rodencal, Joon Tae Kim, Leslie Magtanong, Jonathan Z Long, Scott J Dixon

    Amy Tarangelo ... Scott J Dixon

    Published 24 January 2022

    The tumor suppressor protein p53 inhibits ferroptosis by reducing the consumption of glutathione in nucleotide biosynthesis.

  • Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated human airway cultures
    Open Access
    Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated human airway cultures

    Wenrui Guo, Linsey M Porter, Thomas WM Crozier, Matthew Coates, Akhilesh Jha, Mikel McKie, James A Nathan, Paul J Lehner, Edward JD Greenwood, Frank McCaughan

    Wenrui Guo ... Frank McCaughan

    Published 2 February 2022

    There is an urgent need to develop novel therapeutic strategies to prevent viral transmission and COVID-19 disease—we show that topical application of camostat, a TMPRSS2 inhibitor, could be a simple, safe, and effective strategy for restricting upper airway infection.

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Volume 5, No. 4
April 2022
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