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
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.
Linked datasets 4
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_2_1.fastq.gz | RNA-Seq | 1.9 GB |
| ctrl_3_1.fastq.gz | RNA-Seq | 2.2 GB |
| ctrl_4_1.fastq.gz | RNA-Seq | 1.9 GB |
| rel_2_1.fastq.gz | RNA-Seq | 1.7 GB |
| rel_3_1.fastq.gz | RNA-Seq | 1.9 GB |
| rel_4_1.fastq.gz | RNA-Seq | 2.0 GB |
| SRR25238416_GSM7594884 | RNA-Seq | 3.0 GB |
| SRR25238417_GSM7594883 | RNA-Seq | 2.1 GB |
| SRR25238418_GSM7594882 | RNA-Seq | 2.0 GB |
| SRR25238419_GSM7594881 | RNA-Seq | 1.9 GB |
| SRR25238420_GSM7594880 | RNA-Seq | 1.7 GB |
| SRR25238421_GSM7594879 | RNA-Seq | 1.9 GB |
| SRR25238422_GSM7594878 | RNA-Seq | 2.2 GB |
| SRR25238423_GSM7594877 | RNA-Seq | 1.9 GB |
| SRR25238424_GSM7594876 | RNA-Seq | 1.4 GB |
| sus_1_1.fastq.gz | RNA-Seq | 2.1 GB |
| sus_2_1.fastq.gz | RNA-Seq | 3.0 GB |
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
37 data files
| File | Type | Size |
|---|---|---|
| JR-JC-10_1.fastq.gz | RNA-Seq | 1.7 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-12_1.fastq.gz | RNA-Seq | 1.8 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-15_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-18_1.fastq.gz | RNA-Seq | 1.8 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-4_1.fastq.gz | RNA-Seq | 1.7 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-7_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 |
| SRR29988463_GSM8421731 | RNA-Seq | 1.8 GB |
| SRR29988464_GSM8421730 | RNA-Seq | 1.8 GB |
| SRR29988465_GSM8421729 | RNA-Seq | 1.7 GB |
| SRR29988466_GSM8421728 | RNA-Seq | 1.7 GB |
| SRR29988467_GSM8421727 | RNA-Seq | 1.7 GB |
| SRR29988468_GSM8421726 | RNA-Seq | 1.6 GB |
| SRR29988469_GSM8421725 | RNA-Seq | 1.8 GB |
| SRR29988470_GSM8421724 | RNA-Seq | 1.6 GB |
| SRR29988471_GSM8421723 | RNA-Seq | 1.7 GB |
| SRR29988472_GSM8421722 | RNA-Seq | 1.8 GB |
| SRR29988472.lite | RNA-Seq | 1.8 GB |
| SRR29988473_GSM8421721 | RNA-Seq | 1.7 GB |
| SRR29988474_GSM8421720 | RNA-Seq | 1.7 GB |
| SRR29988475_GSM8421719 | RNA-Seq | 1.7 GB |
| SRR29988476_GSM8421718 | RNA-Seq | 1.8 GB |
| SRR29988477_GSM8421717 | RNA-Seq | 1.7 GB |
| SRR29988478_GSM8421716 | RNA-Seq | 1.6 GB |
| SRR29988479_GSM8421715 | RNA-Seq | 1.7 GB |
| SRR29988480_GSM8421714 | RNA-Seq | 1.8 GB |
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_2.fastq.gz | RNA-Seq | 887.9 MB |
| GFP_3.fastq.gz | RNA-Seq | 1.0 GB |
| SRR29988484_GSM8421737 | RNA-Seq | 913.0 MB |
| SRR29988485_GSM8421736 | RNA-Seq | 832.0 MB |
| SRR29988486_GSM8421735 | RNA-Seq | 820.0 MB |
| SRR29988487_GSM8421734 | RNA-Seq | 1.0 GB |
| SRR29988488_GSM8421733 | RNA-Seq | 887.0 MB |
| SRR29988489_GSM8421732 | RNA-Seq | 890.0 MB |
| Zfp697_1.fastq.gz | RNA-Seq | 820.1 MB |
| Zfp697_2.fastq.gz | RNA-Seq | 832.8 MB |
| Zfp697_3.fastq.gz | RNA-Seq | 913.8 MB |
Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling (Zfp697 transduced primary mouse myotubes ChIP-Seq)
Mus musculus
15 data files
| File | Type | Size |
|---|---|---|
| FLAG_1_S4_1.fastq.gz | ChIP-Seq | 1.2 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 |
| mIgG_CTRL1_S1_1.fastq.gz | ChIP-Seq | 2.5 GB |
| mIgG_CTRL2_S2_1.fastq.gz | ChIP-Seq | 1.8 GB |
| mIgG_CTRL3_S3_1.fastq.gz | ChIP-Seq | 2.7 GB |
| SRR29988222_GSM8421744 | ChIP-Seq | 2.7 GB |
| SRR29988223_GSM8421743 | ChIP-Seq | 1.8 GB |
| SRR29988224_GSM8421742 | ChIP-Seq | 2.5 GB |
| SRR29988225_GSM8421741 | ChIP-Seq | 4.4 GB |
| SRR29988226_GSM8421740 | ChIP-Seq | 3.2 GB |
| SRR29988226.lite | ChIP-Seq | 3.2 GB |
| SRR29988227_GSM8421739 | ChIP-Seq | 3.1 GB |
| SRR29988228_GSM8421738 | ChIP-Seq | 1.2 GB |
Potentially related datasets 9
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
| Accession | Source | Title |
|---|---|---|
| GSE145480 | GSE · GEO GEO ↗ | Rodents as models of human sarcopenia: a comparative analysis reveals conserved modulators of aging-dependent muscle loss |
| GSE210263 | GSE · GEO GEO ↗ | Transcriptomic profiles of muscular dystrophy with myositis (mdm) in extensor digitorum longus, psoas, and soleus muscles from mice |
| GSE143437 | GSE · GEO GEO ↗ | Single-cell transcriptomic atlas of the mouse regenerating muscle tissue |
| GSE114820 | GSE · GEO GEO ↗ | A Transcriptomic Analysis of the Development of Skeletal Muscle Atrophy in Cancer-Cachexia in Tumor-Bearing Mice |
| GSE147127 | GSE · GEO GEO ↗ | Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers |
| GSE273092 | GSE · GEO GEO ↗ | Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling (Zfp697 skeletal muscle knockout RNA-Seq of unloading-reloading protocol) |
| GSE273094 | GSE · GEO GEO ↗ | Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling (Zfp697 transduced primary mouse myotubes ChIP-Seq) |
| GSE237099 | GSE · GEO GEO ↗ | Analysis of skeletal muscle gene expression upon mouse hindlimb unloading and reloading |
| GSE273093 | GSE · GEO GEO ↗ | Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling (Zfp697 transduced primary mouse myotubes RNA-Seq) |
Analysis pipelines 9
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE114820 Data Processing geo_data_processing | — | 4 | GSE114820 |
| GSE143437 scRNA-seq Data Processing geo_data_processing | scRNA-seq | 7 | GSE143437 |
| GSE145480 RNA-seq Data Processing geo_data_processing | RNA-seq | 11 | GSE145480 |
| GSE147127 RNA-seq Data Processing geo_data_processing | RNA-seq | 5 | GSE147127 |
| GSE210263 Data Processing geo_data_processing | — | 10 | GSE210263 |
| GSE237099 RNA-seq Data Processing geo_data_processing | RNA-seq | 3 | GSE237099 |
| GSE273092 RNA-seq Data Processing geo_data_processing | RNA-seq | 3 | GSE273092 |
| GSE273093 RNA-seq Data Processing geo_data_processing | RNA-seq | 3 | GSE273093 |
| GSE273094 ChIP-seq Data Processing geo_data_processing | ChIP-seq | 3 | GSE273094 |
Funding 23 grants
| Grant | Funder |
|---|---|
| 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) |