A Micropeptide Encoded by a Putative Long Non-coding RNA Regulates Muscle Performance

By Douglas M. Anderson, Kelly M. Anderson, Chi-Lun Chang, Catherine A. Makarewich, Benjamin R Nelson, John R. McAnally, P. Kasaragod, J. Shelton, J. Liou, R. Bassel-Duby and 1 more. Cell, 2015

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Summary Functional micropeptides can be concealed within RNAs that appear to be non-coding. We discovered a conserved micropeptide, that we named myoregulin (MLN), encoded by a skeletal muscle-specific RNA annotated as a putative long non-coding RNA. MLN shares structural and functional similarity with phospholamban (PLN) and sarcolipin (SLN), which inhibit SERCA, the membrane pump that controls muscle relaxation by regulating Ca2+ uptake into the sarcoplasmic reticulum (SR). MLN interacts directly with SERCA and impedes Ca2+ uptake into the SR. In contrast to PLN and SLN, which are expressed in cardiac and slow skeletal muscle in mice, MLN is robustly expressed in all skeletal muscle. Genetic deletion of MLN in mice enhances Ca2+ handling in skeletal muscle and improves exercise performance. These findings identify MLN as an important regulator of skeletal muscle physiology and highlight the possibility that additional micropeptides are encoded in the many RNAs currently annotated as non-coding.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b22d2cb95af83872d1e31a2dcb37b59f4e8a4326

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Citations in the corpus

Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. (2016, positive): “Indeed, it has been recently reported that, despite their classification as non-coding molecules, some lncRNAs can code for micropeptides (5).”
CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs (2016, background): “41 In addition, the viral circRNA CCC (covalently closed circular, 220 nt long) was recently found to be fully translated into a 16-kDa highly basic protein in infected rice plants.”
The BIG Data Center: from deposition to integration to translation (2016, background): “Moreover, considering the functional significance of lncRNA-encoded small proteins as reported in (45,46), we developed computational approaches for identification of small proteins in all collected human lncRNAs, identified 9387 lncRNAs potentially encoding small proteins and revealed that 2246 out”
Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels (2019, background): “Deletion of the mouse MLN gene enhances the efficiency of skeletal muscle delivery to Ca2+ and improves exercise capacity [101].”
LncRNA-mediated regulation of cell signaling in cancer (2017, background): “…rest of transcripts are non-coding RNAs (ncRNAs) and they lack the coding potential except for those capable of producing functional small peptides (Anderson et al 2015, Nelson et al 2016). ncRNAs were initially considered as transcriptional noises (Gibb et al 2011), however, it has become…”