Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease

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

Standard

Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease. / Mullari, Meeli; Fossat, Nicolas; Skotte, Niels H; Asenjo-Martinez, Andrea; Humphreys, David T; Bukh, Jens; Kirkeby, Agnete; Scheel, Troels K H; Nielsen, Michael L.

In: Nature Communications, Vol. 14, 4348, 2023.

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

Harvard

Mullari, M, Fossat, N, Skotte, NH, Asenjo-Martinez, A, Humphreys, DT, Bukh, J, Kirkeby, A, Scheel, TKH & Nielsen, ML 2023, 'Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease', Nature Communications, vol. 14, 4348. https://doi.org/10.1038/s41467-023-39936-x

APA

Mullari, M., Fossat, N., Skotte, N. H., Asenjo-Martinez, A., Humphreys, D. T., Bukh, J., Kirkeby, A., Scheel, T. K. H., & Nielsen, M. L. (2023). Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease. Nature Communications, 14, [4348]. https://doi.org/10.1038/s41467-023-39936-x

Vancouver

Mullari M, Fossat N, Skotte NH, Asenjo-Martinez A, Humphreys DT, Bukh J et al. Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease. Nature Communications. 2023;14. 4348. https://doi.org/10.1038/s41467-023-39936-x

Author

Mullari, Meeli ; Fossat, Nicolas ; Skotte, Niels H ; Asenjo-Martinez, Andrea ; Humphreys, David T ; Bukh, Jens ; Kirkeby, Agnete ; Scheel, Troels K H ; Nielsen, Michael L. / Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease. In: Nature Communications. 2023 ; Vol. 14.

Bibtex

@article{cf0587ad045f4baf90ec6f899900e961,
title = "Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease",
abstract = "RNA-binding proteins (RBPs) are key players regulating RNA processing and are associated with disorders ranging from cancer to neurodegeneration. Here, we present a proteomics workflow for large-scale identification of RBPs and their RNA-binding regions in the mammalian brain identifying 526 RBPs. Analysing brain tissue from males of the Huntington's disease (HD) R6/2 mouse model uncovered differential RNA-binding of the alternative splicing regulator RBM5. Combining several omics workflows, we show that RBM5 binds differentially to transcripts enriched in pathways of neurodegeneration in R6/2 brain tissue. We further find these transcripts to undergo changes in splicing and demonstrate that RBM5 directly regulates these changes in human neurons derived from embryonic stem cells. Finally, we reveal that RBM5 interacts differently with several known huntingtin interactors and components of huntingtin aggregates. Collectively, we demonstrate the applicability of our method for capturing RNA interactor dynamics in the contexts of tissue and disease.",
keywords = "Mice, Male, Animals, Humans, Huntington Disease/genetics, Brain/metabolism, RNA-Binding Proteins/genetics, Disease Models, Animal, Mammals/genetics, RNA/metabolism, Huntingtin Protein/genetics, Mice, Transgenic, DNA-Binding Proteins/metabolism, Cell Cycle Proteins/metabolism, Tumor Suppressor Proteins/genetics",
author = "Meeli Mullari and Nicolas Fossat and Skotte, {Niels H} and Andrea Asenjo-Martinez and Humphreys, {David T} and Jens Bukh and Agnete Kirkeby and Scheel, {Troels K H} and Nielsen, {Michael L}",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
doi = "10.1038/s41467-023-39936-x",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease

AU - Mullari, Meeli

AU - Fossat, Nicolas

AU - Skotte, Niels H

AU - Asenjo-Martinez, Andrea

AU - Humphreys, David T

AU - Bukh, Jens

AU - Kirkeby, Agnete

AU - Scheel, Troels K H

AU - Nielsen, Michael L

N1 - © 2023. The Author(s).

PY - 2023

Y1 - 2023

N2 - RNA-binding proteins (RBPs) are key players regulating RNA processing and are associated with disorders ranging from cancer to neurodegeneration. Here, we present a proteomics workflow for large-scale identification of RBPs and their RNA-binding regions in the mammalian brain identifying 526 RBPs. Analysing brain tissue from males of the Huntington's disease (HD) R6/2 mouse model uncovered differential RNA-binding of the alternative splicing regulator RBM5. Combining several omics workflows, we show that RBM5 binds differentially to transcripts enriched in pathways of neurodegeneration in R6/2 brain tissue. We further find these transcripts to undergo changes in splicing and demonstrate that RBM5 directly regulates these changes in human neurons derived from embryonic stem cells. Finally, we reveal that RBM5 interacts differently with several known huntingtin interactors and components of huntingtin aggregates. Collectively, we demonstrate the applicability of our method for capturing RNA interactor dynamics in the contexts of tissue and disease.

AB - RNA-binding proteins (RBPs) are key players regulating RNA processing and are associated with disorders ranging from cancer to neurodegeneration. Here, we present a proteomics workflow for large-scale identification of RBPs and their RNA-binding regions in the mammalian brain identifying 526 RBPs. Analysing brain tissue from males of the Huntington's disease (HD) R6/2 mouse model uncovered differential RNA-binding of the alternative splicing regulator RBM5. Combining several omics workflows, we show that RBM5 binds differentially to transcripts enriched in pathways of neurodegeneration in R6/2 brain tissue. We further find these transcripts to undergo changes in splicing and demonstrate that RBM5 directly regulates these changes in human neurons derived from embryonic stem cells. Finally, we reveal that RBM5 interacts differently with several known huntingtin interactors and components of huntingtin aggregates. Collectively, we demonstrate the applicability of our method for capturing RNA interactor dynamics in the contexts of tissue and disease.

KW - Mice

KW - Male

KW - Animals

KW - Humans

KW - Huntington Disease/genetics

KW - Brain/metabolism

KW - RNA-Binding Proteins/genetics

KW - Disease Models, Animal

KW - Mammals/genetics

KW - RNA/metabolism

KW - Huntingtin Protein/genetics

KW - Mice, Transgenic

KW - DNA-Binding Proteins/metabolism

KW - Cell Cycle Proteins/metabolism

KW - Tumor Suppressor Proteins/genetics

U2 - 10.1038/s41467-023-39936-x

DO - 10.1038/s41467-023-39936-x

M3 - Journal article

C2 - 37468457

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 4348

ER -

ID: 360243786