Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling.

Jorge C Correia, Paulo R Jannig, Maya L Gosztyla, Igor Cervenka, Serge Ducommun, Stine M Præstholm, José M Dias, Kyle D Dumont, Zhengye Liu, Qishan Liang, Daniel Edsgärd, Olof Emanuelsson, Paul Gregorevic, Håkan Westerblad, Tomas Venckunas, Marius Brazaitis, Sigitas Kamandulis, Johanna T Lanner, Ana I Teixeira, Gene W Yeo, Jorge L Ruas

Proceedings of the National Academy of Sciences of the United States of America · 2024 · Vol. 121 (34) · pp. e2319724121

PubMed DOI PMC Full Text

Abstract

Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and satellite and immune cells. Here, we show that the previously uncharacterized gene and protein Zfp697 is a damage-induced regulator of muscle remodeling. Zfp697/ZNF697 expression is transiently elevated during recovery from muscle atrophy or injury in mice and humans. Sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Notably, although Zfp697 is expressed in several cell types in skeletal muscle, myofiber-specific Zfp697 genetic ablation in mice is sufficient to hinder the inflammatory and regenerative response to muscle injury, compromising functional recovery. We show that Zfp697 is an essential mediator of the interferon gamma response in muscle cells and that it functions primarily as an RNA-interacting protein, with a very high number of miRNA targets. This work identifies Zfp697 as an integrator of cell-cell communication necessary for tissue remodeling and regeneration.

Publication Types

["Journal Article"]

Keywords

["RNA-binding protein", "Zfp697", "inflammation", "muscle atrophy", "skeletal muscle"]

MeSH Terms

["Animals", "Mice", "Muscle, Skeletal", "RNA-Binding Proteins", "Humans", "Inflammation", "Mice, Knockout", "Muscular Atrophy", "MicroRNAs", "Mice, Inbred C57BL", "Interferon-gamma"]

Funding

U24 HG009889 NHGRI NIH HHS (United States)

R01 HG004659 NHGRI NIH HHS (United States)

R01 HG011864 NHGRI NIH HHS (United States)

U41 HG009889 NHGRI NIH HHS (United States)

R01 CA273432 NCI NIH HHS (United States)

N/A Myotonic Dystrophy Foundation (MDF)

80358701-03 Vetenskapsrådet (VR)

NNF16OC0020804 Novo Nordisk Fonden (NNF)

NNF22OC0075245 Novo Nordisk Fonden (NNF)

N/A Gösta Fraenckel Foundation for Medical Research

U41HG009889 RF1MH126719 R01NS103172 R01HG004659 and R01HG011864 NIH HHS (United States)

S-MIP-19-54 The Research Council of Lithuania

N/A AFM-Tèlèthon

1117835 and 2017070 National Health and Medical Research Council of Australia

N/A Association for Women in Science (AWIS)

N/A Swedish Society for Medical Research

DGE-2038238 NSF | National Science Foundation Graduate Research Fellowship Program (GRFP)

2019-01282/ 2022-01650 and 207-0479 Vetenskapsrådet (VR)

N/A American Heart Association (AHA)

N/A European Foundation for the Study of Diabetes (EFSD)

2016-00785 Vetenskapsrådet (VR)

N/A Åke Wibergs Foundatio

N/A Swiss National Science Foundation (Switzerland)

Linked Datasets (4)

GSE237099 GSE via ncbi_elink

GEO

Analysis of skeletal muscle gene expression upon mouse hindlimb unloading and reloading

Mus musculus

18 data files

File	Type	Size
ctrl_1_1.fastq.gz	RNA-Seq	1.4 GB
ctrl_1_1.fastq.gz	RNA-Seq	1.4 GB
ctrl_2_1.fastq.gz	RNA-Seq	1.9 GB
ctrl_2_1.fastq.gz	RNA-Seq	1.9 GB
ctrl_3_1.fastq.gz	RNA-Seq	2.2 GB
ctrl_3_1.fastq.gz	RNA-Seq	2.2 GB
ctrl_4_1.fastq.gz	RNA-Seq	1.9 GB
ctrl_4_1.fastq.gz	RNA-Seq	1.9 GB
rel_2_1.fastq.gz	RNA-Seq	1.7 GB
rel_2_1.fastq.gz	RNA-Seq	1.7 GB
rel_3_1.fastq.gz	RNA-Seq	1.9 GB
rel_3_1.fastq.gz	RNA-Seq	1.9 GB
rel_4_1.fastq.gz	RNA-Seq	2.0 GB
rel_4_1.fastq.gz	RNA-Seq	2.0 GB
sus_1_1.fastq.gz	RNA-Seq	2.1 GB
sus_1_1.fastq.gz	RNA-Seq	2.1 GB
sus_2_1.fastq.gz	RNA-Seq	3.0 GB
sus_2_1.fastq.gz	RNA-Seq	3.0 GB

GSE273092 GSE via ncbi_elink

GEO

Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling (Zfp697 skeletal muscle knockout RNA-Seq of unloading-reloading protocol)

Mus musculus

36 data files

File	Type	Size
JR-JC-10_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-10_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-11_1.fastq.gz	RNA-Seq	1.6 GB
JR-JC-11_1.fastq.gz	RNA-Seq	1.6 GB
JR-JC-1_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-1_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-12_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-12_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-13_1.fastq.gz	RNA-Seq	1.6 GB
JR-JC-13_1.fastq.gz	RNA-Seq	1.6 GB
JR-JC-14_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-14_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-15_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-15_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-16_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-16_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-17_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-17_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-18_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-18_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-2_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-2_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-3_1.fastq.gz	RNA-Seq	1.6 GB
JR-JC-3_1.fastq.gz	RNA-Seq	1.6 GB
JR-JC-4_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-4_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-5_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-5_1.fastq.gz	RNA-Seq	1.8 GB
JR-JC-6_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-6_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-7_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-7_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-8_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-8_1.fastq.gz	RNA-Seq	1.7 GB
JR-JC-9_1.fastq.gz	RNA-Seq	1.8 GB
SRR29988472.lite	RNA-Seq	1.8 GB

GSE273093 GSE via ncbi_elink

GEO

Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling (Zfp697 transduced primary mouse myotubes RNA-Seq)

Mus musculus

12 data files

File	Type	Size
GFP_1.fastq.gz	RNA-Seq	890.0 MB
GFP_1.fastq.gz	RNA-Seq	890.0 MB
GFP_2.fastq.gz	RNA-Seq	887.9 MB
GFP_2.fastq.gz	RNA-Seq	887.9 MB
GFP_3.fastq.gz	RNA-Seq	1.0 GB
GFP_3.fastq.gz	RNA-Seq	1.0 GB
Zfp697_1.fastq.gz	RNA-Seq	820.1 MB
Zfp697_1.fastq.gz	RNA-Seq	820.1 MB
Zfp697_2.fastq.gz	RNA-Seq	832.8 MB
Zfp697_2.fastq.gz	RNA-Seq	832.8 MB
Zfp697_3.fastq.gz	RNA-Seq	913.8 MB
Zfp697_3.fastq.gz	RNA-Seq	913.8 MB

GSE273094 GSE via ncbi_elink

GEO

Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling (Zfp697 transduced primary mouse myotubes ChIP-Seq)

Mus musculus

14 data files

File	Type	Size
FLAG_1_S4_1.fastq.gz	ChIP-Seq	1.2 GB
FLAG_1_S4_1.fastq.gz	ChIP-Seq	1.2 GB
FLAG_2_S5_1.fastq.gz	ChIP-Seq	3.1 GB
FLAG_2_S5_1.fastq.gz	ChIP-Seq	3.1 GB
FLAG_3_S6_1.fastq.gz	ChIP-Seq	3.2 GB
Input3_S7_1.fastq.gz	ChIP-Seq	4.4 GB
Input3_S7_1.fastq.gz	ChIP-Seq	4.4 GB
mIgG_CTRL1_S1_1.fastq.gz	ChIP-Seq	2.5 GB
mIgG_CTRL1_S1_1.fastq.gz	ChIP-Seq	2.5 GB
mIgG_CTRL2_S2_1.fastq.gz	ChIP-Seq	1.8 GB
mIgG_CTRL2_S2_1.fastq.gz	ChIP-Seq	1.8 GB
mIgG_CTRL3_S3_1.fastq.gz	ChIP-Seq	2.7 GB
mIgG_CTRL3_S3_1.fastq.gz	ChIP-Seq	2.7 GB
SRR29988226.lite	ChIP-Seq	3.2 GB

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