Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin. / Ghanawi, Hanaa; Hennlein, Luisa; Zare, Abdolhossein; Bader, Jakob; Salehi, Saeede; Hornburg, Daniel; Ji, Changhe; Sivadasan, Rajeeve; Drepper, Carsten; Meissner, Felix; Mann, Matthias; Jablonka, Sibylle; Briese, Michael; Sendtner, Michael.

In: Nucleic Acids Symposium Series, Vol. 49, No. 21, 2021, p. 12284-12305.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ghanawi, H, Hennlein, L, Zare, A, Bader, J, Salehi, S, Hornburg, D, Ji, C, Sivadasan, R, Drepper, C, Meissner, F, Mann, M, Jablonka, S, Briese, M & Sendtner, M 2021, 'Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin', Nucleic Acids Symposium Series, vol. 49, no. 21, pp. 12284-12305. https://doi.org/10.1093/nar/gkab1120

APA

Ghanawi, H., Hennlein, L., Zare, A., Bader, J., Salehi, S., Hornburg, D., Ji, C., Sivadasan, R., Drepper, C., Meissner, F., Mann, M., Jablonka, S., Briese, M., & Sendtner, M. (2021). Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin. Nucleic Acids Symposium Series, 49(21), 12284-12305. https://doi.org/10.1093/nar/gkab1120

Vancouver

Ghanawi H, Hennlein L, Zare A, Bader J, Salehi S, Hornburg D et al. Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin. Nucleic Acids Symposium Series. 2021;49(21):12284-12305. https://doi.org/10.1093/nar/gkab1120

Author

Ghanawi, Hanaa ; Hennlein, Luisa ; Zare, Abdolhossein ; Bader, Jakob ; Salehi, Saeede ; Hornburg, Daniel ; Ji, Changhe ; Sivadasan, Rajeeve ; Drepper, Carsten ; Meissner, Felix ; Mann, Matthias ; Jablonka, Sibylle ; Briese, Michael ; Sendtner, Michael. / Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin. In: Nucleic Acids Symposium Series. 2021 ; Vol. 49, No. 21. pp. 12284-12305.

Bibtex

@article{8f7945e365eb4a12bb1bd8b3d6f3529f,
title = "Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin",
abstract = "Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stress. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing giving rise to a full-length protein and a shorter isoform lacking its N-terminal acidic domain. To investigate functions selectively associated with the full-length hnRNP R isoform, we generated a Hnrnpr knockout mouse (Hnrnpr(tm1a/tm1a)) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnpr(tm1a/tm1a) mice did not show any axonal growth defects but exhibited enhanced accumulation of double-strand breaks and an impaired DNA damage response upon exposure to genotoxic agents. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1-depleted motoneurons were defective in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage where it interacts with gamma-H2AX, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.",
keywords = "NUCLEAR RIBONUCLEOPROTEIN-R, DETERMINING GENE-PRODUCT, ACTIN MESSENGER-RNA, COMET ASSAY, GENOME-WIDE, SPINAL-CORD, YB-1, SMN, INTERACTS, ENRICHMENT",
author = "Hanaa Ghanawi and Luisa Hennlein and Abdolhossein Zare and Jakob Bader and Saeede Salehi and Daniel Hornburg and Changhe Ji and Rajeeve Sivadasan and Carsten Drepper and Felix Meissner and Matthias Mann and Sibylle Jablonka and Michael Briese and Michael Sendtner",
year = "2021",
doi = "10.1093/nar/gkab1120",
language = "English",
volume = "49",
pages = "12284--12305",
journal = "Nucleic acids symposium series",
issn = "0261-3166",
publisher = "Oxford University Press",
number = "21",

}

RIS

TY - JOUR

T1 - Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin

AU - Ghanawi, Hanaa

AU - Hennlein, Luisa

AU - Zare, Abdolhossein

AU - Bader, Jakob

AU - Salehi, Saeede

AU - Hornburg, Daniel

AU - Ji, Changhe

AU - Sivadasan, Rajeeve

AU - Drepper, Carsten

AU - Meissner, Felix

AU - Mann, Matthias

AU - Jablonka, Sibylle

AU - Briese, Michael

AU - Sendtner, Michael

PY - 2021

Y1 - 2021

N2 - Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stress. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing giving rise to a full-length protein and a shorter isoform lacking its N-terminal acidic domain. To investigate functions selectively associated with the full-length hnRNP R isoform, we generated a Hnrnpr knockout mouse (Hnrnpr(tm1a/tm1a)) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnpr(tm1a/tm1a) mice did not show any axonal growth defects but exhibited enhanced accumulation of double-strand breaks and an impaired DNA damage response upon exposure to genotoxic agents. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1-depleted motoneurons were defective in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage where it interacts with gamma-H2AX, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.

AB - Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stress. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing giving rise to a full-length protein and a shorter isoform lacking its N-terminal acidic domain. To investigate functions selectively associated with the full-length hnRNP R isoform, we generated a Hnrnpr knockout mouse (Hnrnpr(tm1a/tm1a)) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnpr(tm1a/tm1a) mice did not show any axonal growth defects but exhibited enhanced accumulation of double-strand breaks and an impaired DNA damage response upon exposure to genotoxic agents. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1-depleted motoneurons were defective in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage where it interacts with gamma-H2AX, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.

KW - NUCLEAR RIBONUCLEOPROTEIN-R

KW - DETERMINING GENE-PRODUCT

KW - ACTIN MESSENGER-RNA

KW - COMET ASSAY

KW - GENOME-WIDE

KW - SPINAL-CORD

KW - YB-1

KW - SMN

KW - INTERACTS

KW - ENRICHMENT

U2 - 10.1093/nar/gkab1120

DO - 10.1093/nar/gkab1120

M3 - Journal article

C2 - 34850154

VL - 49

SP - 12284

EP - 12305

JO - Nucleic acids symposium series

JF - Nucleic acids symposium series

SN - 0261-3166

IS - 21

ER -

ID: 288925690