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Nucl. Acids Res.-2016-In-nar_gkw005.pdf 1,43MB
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1000 Titel
  • Shwachman–Bodian–Diamond syndrome (SBDS) protein deficiency impairs translation re-initiation from C/EBPα and C/EBPβ mRNAs
1000 Autor/in
  1. In, Kyungmin |
  2. Zaini, Mohamad A. |
  3. Müller, Christine |
  4. Warren, Alan J. |
  5. von Lindern, Marieke |
  6. Calkhoven, Cornelis F. |
1000 Erscheinungsjahr 2016
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-01-13
1000 Erschienen in
1000 Quellenangabe
  • 44(9): 4134-4146
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • http://dx.doi.org/10.1093/nar/gkw005 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872075/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Mutations in the Shwachman–Bodian–Diamond Syndrome (SBDS) gene cause Shwachman–Diamond Syndrome (SDS), a rare congenital disease characterized by bone marrow failure with neutropenia, exocrine pancreatic dysfunction and skeletal abnormalities. The SBDS protein is important for ribosome maturation and therefore SDS belongs to the ribosomopathies. It is unknown, however, if loss of SBDS functionality affects the translation of specific mRNAs and whether this could play a role in the development of the clinical features of SDS. Here, we report that translation of the C/EBPα and -β mRNAs, that are indispensible regulators of granulocytic differentiation, is altered by SBDS mutations or knockdown. We show that SBDS function is specifically required for efficient translation re-initiation into the protein isoforms C/EBPα-p30 and C/EBPβ-LIP, which is controlled by a single cis-regulatory upstream open reading frame (uORF) in the 5′ untranslated regions (5′ UTRs) of both mRNAs. Furthermore, we show that as a consequence of the C/EBPα and -β deregulation the expression of MYC is decreased with associated reduction in proliferation, suggesting that failure of progenitor proliferation contributes to the haematological phenotype of SDS. Therefore, our study provides the first indication that disturbance of specific translation by loss of SBDS function may contribute to the development of the SDS phenotype.
1000 Sacherschließung
lokal mutation
lokal ribosomes
lokal diamond
lokal lip
lokal protein isoforms
lokal rna
lokal messenger
lokal protein deficiency
1000 Fachgruppe
  1. Biologie |
  2. Medizin |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/SW4sIEt5dW5nbWlu|https://frl.publisso.de/adhoc/creator/WmFpbmksIE1vaGFtYWQgQS4=|https://frl.publisso.de/adhoc/creator/TcO8bGxlciwgQ2hyaXN0aW5l|https://frl.publisso.de/adhoc/creator/V2FycmVuLCBBbGFuIEou|https://frl.publisso.de/adhoc/creator/dm9uIExpbmRlcm4sIE1hcmlla2U=|https://frl.publisso.de/adhoc/creator/Q2Fsa2hvdmVuLCBDb3JuZWxpcyBGLg==
1000 Förderer
  1. Leibniz Graduate School on Ageing and Age-Related Diseases (LGSA) |
  2. Bloodwise |
  3. Medical Research Council |
  4. Wellcome Trust |
  5. Leibniz Institute on Aging - Fritz Lipmann Institute |
1000 Fördernummer
  1. -
  2. 12048
  3. MC_U105161083
  4. 100140
  5. -
1000 Förderprogramm
  1. -
  2. specialist Programme
  3. -
  4. strategic award; core support
  5. Funding for open access charge
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Leibniz Graduate School on Ageing and Age-Related Diseases (LGSA) |
    1000 Förderprogramm -
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Bloodwise |
    1000 Förderprogramm specialist Programme
    1000 Fördernummer 12048
  3. 1000 joinedFunding-child
    1000 Förderer Medical Research Council |
    1000 Förderprogramm -
    1000 Fördernummer MC_U105161083
  4. 1000 joinedFunding-child
    1000 Förderer Wellcome Trust |
    1000 Förderprogramm strategic award; core support
    1000 Fördernummer 100140
  5. 1000 joinedFunding-child
    1000 Förderer Leibniz Institute on Aging - Fritz Lipmann Institute |
    1000 Förderprogramm Funding for open access charge
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6404211.rdf
1000 Erstellt am 2017-08-28T12:50:27.232+0200
1000 Erstellt von 122
1000 beschreibt frl:6404211
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Wed Jun 20 12:29:49 CEST 2018
1000 Objekt bearb. Wed Jun 20 12:29:49 CEST 2018
1000 Vgl. frl:6404211
1000 Oai Id
  1. oai:frl.publisso.de:frl:6404211 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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