Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells | Zendy

Nicola Guzzi | Zendy; Maciej Cieśla | Zendy; Phuong Cao Thi Ngoc | Zendy; Stefan Lang | Zendy; Sonali Arora | Zendy; Marios Dimitriou | Zendy; Kristýna Pimková | Zendy; Mikael N.E. Sommarin | Zendy; Roberto Munita | Zendy; Michał Lubas | Zendy; Yiting Lim | Zendy; Kazuki Okuyama | Zendy; Shamit Soneji | Zendy; Göran Karlsson | Zendy; Jenny Hansson | Zendy; Göran Jönsson | Zendy; Anders H. Lund | Zendy; Mikael Sigvardsson | Zendy; Eva HellströmLindberg | Zendy; Andrew C. Hsieh | Zendy; Cristian Bellodi | Zendy

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Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells

Author(s) -

Nicola Guzzi,

Maciej Cieśla,

Phuong Cao Thi Ngoc,

Stefan Lang,

Sonali Arora,

Marios Dimitriou,

Kristýna Pimková,

Mikael N.E. Sommarin,

Roberto Munita,

Michał Lubas,

Yiting Lim,

Kazuki Okuyama,

Shamit Soneji,

Göran Karlsson,

Jenny Hansson,

Göran Jönsson,

Anders H. Lund,

Mikael Sigvardsson,

Eva HellströmLindberg,

Andrew C. Hsieh,

Cristian Bellodi

Publication year - 2018

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2018.03.008

Subject(s) - biology , translation (biology) , stem cell , transfer rna , microbiology and biotechnology , embryonic stem cell , epigenetics , translational regulation , rna binding protein , rna , protein biosynthesis , genetics , messenger rna , gene

Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ "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 Ψ in directing translation control in stem cells with important implications for development and disease.

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