RNA Biology
- TERRA promotes telomerase‐mediated telomere elongation in Schizosaccharomyces pombe
- Martin Moravec1,
- Harry Wischnewski1,†,
- Amadou Bah1,†,
- Yan Hu2,
- Na Liu2,
- Lorenzo Lafranchi1,
- Megan C King2 and
- Claus M Azzalin*,1
- 1Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich, Switzerland
- 2Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA
- ↵*Corresponding author. Tel: +41 44 633 4410; Fax: +41 44 632 1298; E‐mail: claus.azzalin{at}bc.biol.ethz.ch
↵† These authors contributed equally to this work
In S. pombe, shortened telomeres produce elevated levels of the lncRNA TERRA, which associates with telomerase and promotes telomerase recruitment and telomere elongation in cis. This is the first direct evidence that TERRA is a positive regulator of telomerase in an organism with human‐like telomeres.
Synopsis
In S. pombe, shortened telomeres produce elevated levels of the lncRNA TERRA, which associates with telomerase and promotes telomerase recruitment and telomere elongation in cis. This is the first direct evidence that TERRA is a positive regulator of telomerase in an organism with human‐like telomeres.
Shortened telomeres produce elevated levels of the TERRA lncRNA in S. pombe.
Polyadenylated TERRA molecules largely devoid of telomeric repeats interact with telomerase.
Experimentally induced telomere transcription leads to telomerase‐mediated telomere elongation in cis.
EMBO Reports (2016) 17: 999–1012
- Received November 5, 2015.
- Revision received April 6, 2016.
- Accepted April 7, 2016.
- © 2016 The Authors
- The AS‐RBM15 lncRNA enhances RBM15 protein translation during megakaryocyte differentiation
- Ngoc‐Tung Tran1,
- Hairui Su1,
- Alireza Khodadadi‐Jamayran1,
- Shan Lin2,
- Li Zhang1,
- Dewang Zhou1,
- Kevin M Pawlik1,
- Tim M Townes1,
- Yabing Chen3,4,
- James C Mulloy2 and
- Xinyang Zhao*,1
- 1Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA
- 2Cincinnati Children's Hospital, Cincinnati, OH, USA
- 3Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA
- 4Research Department, Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA
- ↵*Corresponding author. Tel: +1 205 975 5016; E‐mail: Zhaox88{at}uab.edu
The lncRNA AS‐RBM15 is transcriptionally upregulated by RUNX1 and enhances RBM15 protein translation via its overlapping region with the RBM15 5′UTR.
Synopsis
The lncRNA AS‐RBM15 is transcriptionally up‐regulated by RUNX1 and enhances RBM15 protein translation via its overlapping region with the RBM15 5′UTR.
AS‐RBM15 activated by the transcription factor RUNX1 promotes megakaryocyte differentiation via enhancing RBM15 protein translation.
Exon 1 of AS‐RBM15, which overlaps with the 5′UTR of RBM15 mRNA, is sufficient to enhance 5′cap‐dependent RBM15 protein translation.
The cytoplasmic fraction of AS‐RBM15 is increased in response to megakaryocyte differentiation signals.
EMBO Reports (2016) 17: 887–900
- Received December 27, 2015.
- Revision received March 29, 2016.
- Accepted March 30, 2016.
- © 2016 The Authors
- miR‐10b expression in breast cancer stem cells supports self‐renewal through negative PTEN regulation and sustained AKT activation
- Ivan Bahena‐Ocampo1,
- Magali Espinosa1,
- Gisela Ceballos‐Cancino1,
- Floria Lizarraga1,
- Denise Campos‐Arroyo1,
- Angela Schwarz1,
- Vilma Maldonado1 and
- Jorge Melendez‐Zajgla*,1
- 1Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Mexico City, Mexico
- ↵*Corresponding author. Tel: +52 5553 501920; E‐mail: jmelendez{at}inmegen.gob.mx
The oncogenic microRNA miR‐10b regulates the stem phenotype of breast cancer cells. This is accomplished by targeting the PTEN tumor suppressor gene, which in turns increases the activation of Akt.
Synopsis
The oncogenic microRNA miR‐10b regulates the stem phenotype of breast cancer cells. This is accomplished by targeting the PTEN tumor suppressor gene, which in turns increases the activation of Akt.
miR‐10b is overexpressed in breast cancer stem cells.
It regulates the number of stem cells and stem cell markers in breast cancer cell lines.
miR‐10b targets PTEN, which in turn activates Akt. PTEN is needed for the effects of miR‐10b on the stem phenotype.
EMBO Reports (2016) 17: 648–658
- Received May 20, 2015.
- Revision received February 20, 2016.
- Accepted March 4, 2016.
- © 2016 The Authors
- miR‐515‐5p controls cancer cell migration through MARK4 regulation
- Olivier E Pardo*,1,†,
- Leandro Castellano1,†,
- Catriona E Munro1,†,
- Yili Hu2,
- Francesco Mauri1,
- Jonathan Krell1,
- Romain Lara1,
- Filipa G Pinho1,
- Thameenah Choudhury1,
- Adam E Frampton1,
- Loredana Pellegrino1,
- Dmitry Pshezhetskiy1,
- Yulan Wang2,
- Jonathan Waxman1,
- Michael J Seckl*,1,3 and
- Justin Stebbing*,1,3
- 1Department of Surgery & Cancer, Division of Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College Hammersmith Hospital Campus, London, UK
- 2Department of Oncology, Imperial College Healthcare NHS Trust Charing Cross Hospital, London, UK
- 3Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences, Wuhan, China
- ↵*
Corresponding author. Tel: +44 2075942814; E‐mail: o.pardo{at}imperial.ac.uk
Corresponding author. Tel: +44 2033111421; E‐mail: m.seckl{at}imperial.ac.uk
Corresponding author. Tel: +44 203 3118295; E‐mail: j.stebbing{at}imperial.ac.uk
↵† These authors contributed equally to this work
miR‐515‐5p inhibits cancer progression, cell migration and metastasis through its direct target MARK4, a regulator of the cytoskeleton and cell motility. Moreover, reduced miR‐515‐5p and increased MARK4 levels in metastatic lung and breast cancer correlate with poor patient prognosis.
Synopsis
miR‐515‐5p inhibits cancer progression, cell migration and metastasis through its direct target MARK4, a regulator of the cytoskeleton and cell motility. Moreover, reduced miR‐515‐5p and increased MARK4 levels in metastatic lung and breast cancer correlate with poor patient prognosis.
MARK4 down‐regulation promotes microtubule polymerisation.
Increased cell spreading downstream of miR‐515‐5p overexpression or MARK4 silencing hinders cell motility and invasiveness.
miR‐515‐5p overexpression or MARK4 silencing prevent organ colonisation by circulating tumour cells.
MARK4 inhibitors may represent novel therapeutic agents to control cancer dissemination.
EMBO Reports (2016) 17: 570–584
- Received July 3, 2015.
- Revision received December 22, 2015.
- Accepted January 13, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development
- 1Division of Materials Science and Chemical Engineering, Faculty of Engineering, Yokohama National University, Yokohama Kanagawa, Japan
- 2Division of Materials Science and Chemical Engineering, Graduate School of Engineering Yokohama National University, Yokohama Kanagawa, Japan
- 3Mass Spectrometric Unit, RIKEN Center for Developmental Biology, Kobe Hyogo, Japan
- 4Division of Mammalian Development, National Institute of Genetics, Mishima Shizuoka, Japan
- 5National Cerebral and Cardiovascular Center, Suita Osaka, Japan
- ↵*
Corresponding author. Tel: +81 45 339 4264; E‐mail: atsuzuki{at}ynu.ac.jp
Corresponding author. Tel: +81 55 981 6829; E‐mail: ysaga{at}lab.nig.ac.jp
The NANOS2–Dead end1 (DND1) complex is required for the differentiation of mouse male germ cells. DND1 associates with the CCR4–NOT deadenylase complex via NANOS2 and promotes the degradation of specific NANOS2‐associated mRNAs.
Synopsis
The NANOS2–Dead end1 (DND1) complex is required for the differentiation of mouse male germ cells. DND1 associates with the CCR4–NOT deadenylase complex via NANOS2, and promotes the degradation of specific NANOS2‐associated mRNAs.
Mouse NANOS2 directly interacts with DND1.
DND1 co‐localizes with NANOS2 in P‐bodies of male embryonic germ cells.
DND1 is essential for NANOS2 binding to certain target RNAs.
EMBO Reports (2016) 17: 37–46
- Received June 10, 2015.
- Revision received October 21, 2015.
- Accepted October 27, 2015.
- © 2015 The Authors
- The pathogenicity of splicing defects: mechanistic insights into pre‐mRNA processing inform novel therapeutic approaches
- 1Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
- 2Universitat Pompeu‐Fabra, Barcelona, Spain
- 3Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
- ↵*Corresponding author. Tel: +34 93 316 01 56; E‐mail: juan.valcarcel{at}crg.eu
↵† These authors contributed equally to this study
Mutations affecting pre‐mRNA splicing have been linked to various human pathologies. This review discusses recent insights into the molecular mechanisms of disease‐causing splicing defects, which may inform future therapies and enhance our understanding of complex splicing processes.
EMBO Reports (2015) 16: 1640–1655
- Received July 30, 2015.
- Revision received October 9, 2015.
- Accepted October 12, 2015.
- © 2015 The Authors
- A conformational RNA zipper promotes intron ejection during non‐conventional XBP1 mRNA splicing
- 1Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA
- 2Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA
- ↵*
Corresponding author. Tel: +1 415 476 4636; E‐mail: jirka{at}walterlab.ucsf.edu
Corresponding author. Tel: +1 415 476 4636; E‐mail: diego.acosta-alvear{at}ucsf.edu
Corresponding author. Tel: +1 415 476 4636; E‐mail: peter{at}walterlab.ucsf.edu
↵† These authors contributed equally to this work
Unconventional splicing of XBP1 mRNA by IRE1 and tRNA ligase is a key regulatory step in the UPR. This study shows that RNA‐intrinsic conformational changes are a prerequisite for the completion of the reaction, defining an active role for XBP1 mRNA in its splicing reaction.
Synopsis
Unconventional splicing of XBP1 mRNA by IRE1 and tRNA ligase is a key regulatory step in the UPR. This study shows that RNA‐intrinsic conformational changes are a prerequisite for the completion of the reaction, defining an active role for XBP1 mRNA in its splicing reaction.
Conserved RNA‐intrinsic conformational changes promote intron‐ejection after IRE1‐mediated cleavage of the XBP1 mRNA.
Base‐pairing of the XBP1 mRNA exons by a zipper‐like mechanism is important to complete the splicing reaction by tRNA ligases.
Exon zippering is an important component that ensures the efficiency and fidelity of XBP1 splicing in living cells.
EMBO Reports (2015) 16: 1688–1698
- Received July 1, 2015.
- Revision received September 17, 2015.
- Accepted September 18, 2015.
- © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- A lncRNA to repair DNA
In this issue of EMBO Reports, Misteli and colleagues show that the lncRNA DDSR1 promotes DNA repair by homologous recombination by sequestering BRCA1 and hnRNPUL1.
- © 2015 The Authors
- A BRCA1‐interacting lncRNA regulates homologous recombination
- Vivek Sharma*,1,
- Simran Khurana1,
- Nard Kubben1,
- Kotb Abdelmohsen2,
- Philipp Oberdoerffer1,
- Myriam Gorospe2 and
- Tom Misteli*,1
- 1National Cancer Institute, NIH, Bethesda, MD, USA
- 2National Institute on Aging, NIH, Baltimore, MD, USA
- ↵*
Corresponding author. Tel: +1 3014335470; E‐mail: viveksharmabt{at}gmail.com
Corresponding author. Tel: +1 3014023959; E‐mail: mistelit{at}mail.nih.gov
This study establishes a role for the lncRNA DDSR1 in maintaining genome stability. DDSR1 promotes homologous recombination by regulating recruitment of DNA repair factors to DSB after DNA damage.
Synopsis
This study establishes a role for the lncRNA DDSR1 in maintaining genome stability. DDSR1 promotes homologous recombination by regulating recruitment of DNA repair factors to DSB after DNA damage.
The lncRNA DDSR1 is induced upon DNA damage and interacts with BRCA1 and the RNA‐binding repair protein hnRNPUL1.
DDSR1 and hnRNPUL1 interact to form a complex which prevents BRCA1 from promiscuous DNA binding and fine‐tunes the recruitment of BRCA1 to DSBs upon DNA damage.
Absence of DDSR1 or hnRNPUL1 during DNA damage leads to increased recruitment of RAP80 and BRCA1 to DSBs to limit HR.
EMBO Reports (2015) 16: 1520–1534
- Received March 23, 2015.
- Revision received August 21, 2015.
- Accepted August 25, 2015.
- Published 2015. This article is a U.S. Government work and is in the public domain in the USA
- miR‐9‐5p suppresses pro‐fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2
- Marta Fierro‐Fernández1,
- Óscar Busnadiego1,
- Pilar Sandoval1,
- Cristina Espinosa‐Díez1,
- Eva Blanco‐Ruiz1,
- Macarena Rodríguez2,
- Héctor Pian2,
- Ricardo Ramos3,
- Manuel López‐Cabrera1,
- Maria Laura García‐Bermejo2 and
- Santiago Lamas*,1
- 1Department of Cell Biology and Immunology, Centro de Biología Molecular “Severo Ochoa” (CBMSO), Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, Madrid, Spain
- 2Department of Pathology, Hospital Universitario “Ramón y Cajal”, IRYCIS, Madrid, Spain
- 3Genomic Facility, Parque Científico de Madrid, Madrid, Spain
- ↵*Corresponding author. Tel: +34 911964455; Fax: +34 911964420; E‐mail: slamas{at}cbm.csic.es
miR‐9‐5p is discovered as an anti‐fibrotic miRNA that targets TGBR2 and NOX4 to inhibit the transformation of fibroblasts into myofibroblasts. TGF‐β1 itself is pro‐fibrogenic, but promotes miR‐9‐5p expression, thus inducing inhibition of its own pro‐fibrogenic role.
Synopsis
miR‐9‐5p is discovered as an anti‐fibrotic miRNA that targets TGBR2 and NOX4 to inhibit the transformation of fibroblasts into myofibroblasts. TGF‐β1 itself is pro‐fibrogenic, but promotes miR‐9‐5p expression, thus inducing inhibition of its own pro‐fibrogenic role.
Reactive oxygen species and TGF‐β1 induce miR‐9‐5p expression.
miR‐9‐5p inhibits TGFBR2 and NOX4 expression by binding to their 3′‐UTRs.
miR‐9‐5p inhibits TGF‐β‐mediated pro‐fibrogenic signaling in human lung fibroblasts and attenuates the development of experimental pulmonary fibrosis.
Peritoneal mesothelial fibrogenesis is also significantly reduced by miR‐9‐5p.
EMBO Reports (2015) 16: 1358–1377
- Received May 28, 2015.
- Revision received July 17, 2015.
- Accepted July 20, 2015.
- © 2015 The Authors
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