CircTmeff1 Promotes Muscle Atrophy by Interacting with TDP‐43 and Encoding A Novel TMEFF1‐339aa Protein

Chen, Rui; Yang, Tingting; Jin, Bing; Xu, Wanru; Yan, Yuwei; Wood, Nathanael; Lehmann, H. Immo; Wang, Siqi; Zhu, Xiaolan; Yuan, Weilin; Chen, Hongjian; Liu, Zhengyu; Li, Guoping; Bowen, T. Scott; Jin, Li; Xiao, Junjie

doi:10.1002/advs.202206732

Cited by 9 publications

(1 citation statement)

References 72 publications

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“…Skeletal muscle atrophy is a common clinical feature of many acute and chronic diseases. Chen et al (2023b) analyzed the expression profile of circRNA and showed that circRNA was involved in the pathophysiological process of muscle atrophy. CircTmeff1 was identified as a potential circRNA candidate affecting muscle atrophy.…”

Section: Circrna-encoded Proteins In Other Systemsmentioning

confidence: 99%

Newly discovered circRNAs encoding proteins: recent progress

Shi,

Liao,

et al. 2023

Front. Genet.

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Circular RNA (circRNA) is a special class of noncoding RNA molecules and the latest research hotspot in the field of RNA. CircRNA molecules have a closed loop structure, which is not affected by RNA exonuclease and has the characteristics of more stable expression. Previous studies have shown that circRNA molecules are rich in microRNA (miRNA) binding sites and act as miRNA sponges in cells. By interacting with miRNAs associated with tumors and other diseases, circRNAs play an important regulatory role. However, circRNAs have recently been found to have small open reading frames that enable them to encode peptides/proteins. These proteins have been reported to play an important role in the mechanism of regulation of a variety of diseases and have great potential in the diagnosis and treatment of diseases. In this review, we summarize the mechanism of action of the newly discovered circRNA-coding proteins since 2022 and briefly describe their research process. In addition, we also discuss the prediction model of the functional sites and encoded proteins of circRNAs, which provides a potential idea for future research on circRNAs.

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Section: Circrna-encoded Proteins In Other Systemsmentioning

confidence: 99%

Newly discovered circRNAs encoding proteins: recent progress

Shi,

Liao,

et al. 2023

Front. Genet.

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CircTmeff1 Promotes Muscle Atrophy by Interacting with TDP‐43 and Encoding A Novel TMEFF1‐339aa Protein

et al. 2023

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Skeletal muscle atrophy is a common clinical feature of many acute and chronic conditions. Circular RNAs (circRNAs) are covalently closed RNA transcripts that are involved in various physiological and pathological processes, but their role in muscle atrophy remains unknown. Global circRNA expression profiling indicated that circRNAs are involved in the pathophysiological processes of muscle atrophy. circTmeff1 is identified as a potential circRNA candidate that influences muscle atrophy. It is further identified that circTmeff1 is highly expressed in multiple types of muscle atrophy in vivo and in vitro. Moreover, the overexpression of circTmeff1 triggers muscle atrophy in vitro and in vivo, while the knockdown of circTmeff1 expression rescues muscle atrophy in vitro and in vivo. In particular, the knockdown of circTmeff1 expression partially rescues muscle mass in mice during established atrophic settings. Mechanistically, circTmeff1 directly interacts with TAR DNA-binding protein 43 (TDP-43) and promotes aggregation of TDP-43 in mitochondria, which triggers the release of mitochondrial DNA (mtDNA) into cytosol and activation of the cyclic GMP-AMP synthase (cGAS)/ stimulator of interferon genes (STING) pathway. Unexpectedly, TMEFF1-339aa is identified as a novel protein encoded by circTmeff1 that mediates its pro-atrophic effects. Collectively, the inhibition of circTmeff1 represents a novel therapeutic approach for multiple types of skeletal muscle atrophy.

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EIF4A3‐Induced Circular RNA CircDdb1 Promotes Muscle Atrophy through Encoding a Novel Protein CircDdb1‐867aa

Zhu,

Yang,

Zheng

et al. 2024

Advanced Science

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Little is known about if and how circular RNAs (circRNAs) are involved in skeletal muscle atrophy. Here a conserved circular RNA Damage‐specific DNA binding protein 1 (circDdb1), derived from the host gene encoding Damage‐specific DNA binding protein 1 (DDB1), as a mechanism of muscle atrophy is identified. circDdb1 expression is markedly increased in a variety of muscle atrophy types in vivo and in vitro, and human aging muscle. Both in vivo and in vitro, ectopic expression of circDdb1 causes muscle atrophy. In contrast, multiple forms of muscle atrophy caused by dexamethasone, tumor necrosis factor‐alpha (TNF‐α), or angiotensin II (Ang II) in myotube cells, as well as by denervation, angiotensin II, and immobility in mice, are prevented by circDdb1 inhibition. Eukaryotic initiation factor 4A3 (EIF4A3) is identified as a regulator of circDdb1 expression in muscle atrophy, whereas circDdb1 encodes a novel protein, circDdb1‐867aa. circDdb1‐867aa binds with and increases the phosphorylation level of eukaryotic elongation factor 2 (eEF2) at Thr56 to reduce protein translation and promote muscle atrophy. In summary, these findings establish circDdb1 as a shared regulator of muscle atrophy across multiple diseases and a potential therapeutic target.

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CircTmeff1 Promotes Muscle Atrophy by Interacting with TDP‐43 and Encoding A Novel TMEFF1‐339aa Protein

Cited by 9 publications

References 72 publications

Newly discovered circRNAs encoding proteins: recent progress

Newly discovered circRNAs encoding proteins: recent progress

CircTmeff1 Promotes Muscle Atrophy by Interacting with TDP‐43 and Encoding A Novel TMEFF1‐339aa Protein

EIF4A3‐Induced Circular RNA CircDdb1 Promotes Muscle Atrophy through Encoding a Novel Protein CircDdb1‐867aa

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