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. 2020 Feb 7;7:394.
doi: 10.3389/fcell.2019.00394. eCollection 2019.

Non-coding RNAs Shaping Muscle

Free PMC article

Non-coding RNAs Shaping Muscle

Julie Martone et al. Front Cell Dev Biol. .
Free PMC article


In 1957, Francis Crick speculated that RNA, beyond its protein-coding capacity, could have its own function. Decade after decade, this theory was dramatically boosted by the discovery of new classes of non-coding RNAs (ncRNAs), including long ncRNAs (lncRNAs) and circular RNAs (circRNAs), which play a fundamental role in the fine spatio-temporal control of multiple layers of gene expression. Recently, many of these molecules have been identified in a plethora of different tissues, and they have emerged to be more cell-type specific than protein-coding genes. These findings shed light on how ncRNAs are involved in the precise tuning of gene regulatory mechanisms governing tissues homeostasis. In this review, we discuss the recent findings on the mechanisms used by lncRNAs and circRNAs to sustain skeletal and cardiac muscle formation, paying particular attention to the technological developments that, over the last few years, have aided their genome-wide identification and study. Together with lncRNAs and circRNAs, the emerging contribution of Piwi-interacting RNAs and transfer RNA-derived fragments to myogenesis will be also discussed, with a glimpse on the impact of their dysregulation in muscle disorders, such as myopathies, muscle atrophy, and rhabdomyosarcoma degeneration.

Keywords: Piwi-interacting RNAs; circRNAs; circular RNAs; lncRNAs; long non-coding RNAs; myogenesis; non-coding RNAs; transfer RNA-derived fragments.


Figure 1
Figure 1
Functional roles of tRNA-derived fragments (tRFs) in skeletal and cardiac muscle homeostasis. Central panel: tRNAs are processed into different categories of tRFs by enzymatic cleavage on specific sites (indicated with dashed lines). (A) tRNA fragments can target the 3′ untranslated region (UTR) of protein-coding transcripts (e.g., Kassiri et al., 2009) and regulate their stability and translation efficiency with a microRNA (miRNA)-like mechanism. (B) Massive cleavage of specific tRNA species in stress conditions induces a rapid translational blockade. (C) Accumulation of tRFs in the sperm is responsible for the non-genetic transmission of myocardial hypertrophy phenotypic traits in the offspring. (D) tRFs produced from myoblasts are selectively loaded in extracellular vesicles and could act as mediators of cell-to-cell communication.

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