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

Correia, Jorge C.; Jannig, Paulo R.; Gosztyla, Maya L.; Červenka, Igor; Ducommun, Serge; Præstholm, Stine M.; Dumont, Kyle; Liu, Zhengye; Liang, Qishan; Edsgärd, Daniel; Emanuelsson, Olof; Gregorevic, Paul; Westerblad, Håkan; Venckūnas, Tomas; Brazaitis, Marius; Kamandulis, Sigitas; Lanner, Johanna T.; Yeo, G; Ruas, Jorge L.

doi:10.1101/2023.06.12.544338

Cited by 2 publications

(1 citation statement)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…p<0.05) was: 30 minutes -64 upregulated, 5 downregulated; 3 hours -1281 upregulated, 1298 downregulated; 8 hours -1764 upregulated, 1253 downregulated; and 24 hours -751 upregulated, 445 downregulated (Figure 2B). As anticipated, we noted substantial expression changes in genes previously recognized as responsive to RE and/or important for muscle remodeling (Figure 2C) 25,26,59,60 . Of all upregulated genes across the 24-hour recovery period in the RE group, 46% were differentially expressed at two or more time points while the proportion was 34% for downregulated genes.…”

Section: Differentially Expressed Genes (Degs) Peaked 8 Hours After R...supporting

confidence: 80%

The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle ImplicatesMYCas a Hypertrophic Regulator That is Sufficient for Growth

Edman,

Jones,

Jannig

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Molecular control of recovery after exercise in muscle is temporally dynamic. A time course of biopsies around resistance exercise (RE) combined with -omics is necessary to better comprehend the molecular contributions of skeletal muscle adaptation in humans. Vastus lateralis biopsies before and 30 minutes, 3-, 8-, and 24-hours after acute RE were collected. A time-point matched biopsy-only group was also included. RNA-sequencing defined the transcriptome while DNA methylomics and computational approaches complemented these data. The post-RE time course revealed: 1) DNA methylome responses at 30 minutes corresponded to upregulated genes at 3 hours, 2) a burst of translation- and transcription-initiation factor-coding transcripts occurred between 3 and 8 hours, 3) global gene expression peaked at 8 hours, 4) ribosome-related genes dominated the mRNA landscape between 8 and 24 hours, 5) methylation-regulated MYC was a highly influential transcription factor throughout the 24-hour recovery and played a primary role in ribosome-related mRNA levels between 8 and 24 hours. The influence of MYC in human muscle adaptation was strengthened by transcriptome information from acute MYC overexpression in mouse muscle. To test whether MYC was sufficient for hypertrophy, we generated a muscle fiber-specific doxycycline inducible model of pulsatile MYC induction. Periodic 48-hour pulses of MYC over 4 weeks resulted in higher muscle mass and fiber size in the soleus of adult female mice. Collectively, we present a temporally resolved resource for understanding molecular adaptations to RE in muscle and reveal MYC as a regulator of RE-induced mRNA levels and hypertrophy.

show abstract

Section: Differentially Expressed Genes (Degs) Peaked 8 Hours After R...supporting

confidence: 80%

The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle ImplicatesMYCas a Hypertrophic Regulator That is Sufficient for Growth

Edman,

Jones,

Jannig

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

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

Correia,

Jannig,

Gosztyla

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 2 publications

References 58 publications

The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle ImplicatesMYCas a Hypertrophic Regulator That is Sufficient for Growth

The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle ImplicatesMYCas a Hypertrophic Regulator That is Sufficient for Growth

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

Contact Info

Product

Resources

About