PuSH - Publication Server of Helmholtz Zentrum München: Depletion of the RNA-binding protein PURA triggers changes in posttranscriptional gene regulation and loss of P-bodies.

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Molitor, L. ; Klostermann, M.* ; Bacher, S. ; Merl-Pham, J. ; Spranger, N. ; Burczyk, S.* ; Ketteler, C. ; Rusha, E. ; Tews, D.* ; Pertek, A. ; Proske, M. ; Busch, A.* ; Reschke, S.* ; Feederle, R. ; Hauck, S.M. ; Blum, H.* ; Drukker, M. ; Fischer-Posovszky, P.* ; König, J.* ; Zarnack, K.* ; Niessing, D.

Depletion of the RNA-binding protein PURA triggers changes in posttranscriptional gene regulation and loss of P-bodies.

Nucleic Acids Res. 51, 1297-1316 (2023)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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The RNA-binding protein PURA has been implicated in the rare, monogenetic, neurodevelopmental disorder PURA Syndrome. PURA binds both DNA and RNA and has been associated with various cellular functions. Only little is known about its main cellular roles and the molecular pathways affected upon PURA depletion. Here, we show that PURA is predominantly located in the cytoplasm, where it binds to thousands of mRNAs. Many of these transcripts change abundance in response to PURA depletion. The encoded proteins suggest a role for PURA in immune responses, mitochondrial function, autophagy and processing (P)-body activity. Intriguingly, reduced PURA levels decrease the expression of the integral P-body components LSM14A and DDX6 and strongly affect P-body formation in human cells. Furthermore, PURA knockdown results in stabilization of P-body-enriched transcripts, whereas other mRNAs are not affected. Hence, reduced PURA levels, as reported in patients with PURA Syndrome, influence the formation and composition of this phase-separated RNA processing machinery. Our study proposes PURA Syndrome as a new model to study the tight connection between P-body-associated RNA regulation and neurodevelopmental disorders.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Single-stranded-dna; Postnatal Brain-development; Messenger-rna; Stress Granule; Alpha; Reveals; Transcription; Association; Repression; Complexes

ISSN (print) / ISBN 0305-1048

e-ISSN 1362-4962

Journal Nucleic Acids Research

Quellenangaben Volume: 51, Issue: 3, Pages: 1297-1316

Publisher Oxford University Press

Publishing Place Great Clarendon St, Oxford Ox2 6dp, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Structural Biology (STB)
CF Metabolomics & Proteomics (CF-MPC)
CF Monoclonal Antibodies (CF-MAB)
Institute of Stem Cell Research (ISF)

Grants Ulm University
Science Award of the Care-for-Rare Foundation
SPP 1935
SFB 902
Heisenberg professorship
Deutsche Forschungsgemeinschaft (DFG)