mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide

Hidden Peptides Encoded by Putative Noncoding RNAs

“…These animals manifest no apparent developmental abnormalities, but their skeletal muscle shows enhanced regeneration capacity after acute injury as well as enhanced mTORC1 activation. These observations are consistent with the abundance of Spar mRNA in skeletal muscle of wild-type mice as well as with the fact that amino acid-induced mTORC1 activation is required for regeneration after muscle injury, and they suggest that mTORC1 activation is precisely regulated by the SPAR polypeptide in a tissue-specific manner (Matsumoto et al, 2017).…”

“…Of note, SPAR had no obvious effect on lysosomal acidification but was found to inhibit mTORC1 activation by amino acids through regulation of the v-ATPase-Ragulator supercomplex (Fig. 3E) (Matsumoto et al, 2017).…”

“…Peptidomics is a modified form of proteomics that combines MS and computational prediction (Fig. 2D) (Ma et al, 2016;Matsumoto et al, 2017;Slavoff et al, 2013). Peptides are usually concentrated with the use of a molecular weight cutoff filter (MWCO) or sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in order to reduce the background signal due to larger annotated proteins.…”

“…Although lncRNAs do not harbor apparent open reading frames (ORFs) for proteins of >100 amino acids, recent studies have identified a subset of lncRNAs that actually encode polypeptides of <100 amino acids (Fig. 1A) (Anderson et al, 2015;Kondo et al, 2010;Matsumoto et al, 2017;Nelson et al, 2016;Pauli et al, 2014).…”

LncRNA-encoded peptides: More than translational noise?

“…This regulatory network has now been extended by the work of Matsumoto et al who demonstrate that SPAR, a polypeptide translated from lncRNA LINC00961, inhibits amino acid-mediated mTORC1 activation at the lysosomal membrane [7]. SPAR was discovered by proteomics aimed at identifying polypeptides encoded by lncRNAs.…”