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Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
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2018 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 173, no 5, p. 1204-+Article in journal (Refereed) Published
Abstract [en]

Pseudouridylation (J) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of J remains poorly understood. Here, we show that a J-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the J "writer PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein biosynthesis and defective germ layer specification. Remarkably, dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes. Our findings unveil a critical function of J in directing translation control in stem cells with important implications for development and disease.

Place, publisher, year, edition, pages
CELL PRESS , 2018. Vol. 173, no 5, p. 1204-+
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-148385DOI: 10.1016/j.cell.2018.03.008ISI: 000432471700016PubMedID: 29628141OAI: oai:DiVA.org:liu-148385DiVA, id: diva2:1218962
Note

Funding Agencies|DOD PCRP [PC150946]; AACR-Bristol-Meyer Squib Oncology Fellowship in Clinical Cancer Research; NIH-NCI [1K08CA175154]; Burroughs Wellcome Fund Career Award for Medical Scientists; V Foundation Scholar Award; AACR-Bayer NextGen Grant for Transformative Cancer Research; Swedish Foundations Starting Grant (SFSG); StemTherapy; Swedish Research Council (Vetenskapsradet) [E0236201]; Swedish Cancer Society (Cancerfonden) [CAN2014/572]

Available from: 2018-06-15 Created: 2018-06-15 Last updated: 2018-06-15

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CiteExportLink to record
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Citation style
  • apa
  • harvard1
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  • modern-language-association-8th-edition
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  • Other style
More styles
Language
  • de-DE
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  • sv-SE
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