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

@article{Matsumoto2017mTORC1AM,
  title={mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide},
  author={Akinobu Matsumoto and Alessandra Pasut and Masaki Matsumoto and Riu Yamashita and Jacqueline Fung and Emanuele Monteleone and Alan Saghatelian and Keiichi I. Nakayama and John Gerard Clohessy and Pier Paolo Pandolfi},
  journal={Nature},
  year={2017},
  volume={541},
  pages={228-232}
}
Although long non-coding RNAs (lncRNAs) are non-protein-coding transcripts by definition, recent studies have shown that a fraction of putative small open reading frames within lncRNAs are translated. However, the biological significance of these hidden polypeptides is still unclear. Here we identify and functionally characterize a novel polypeptide encoded by the lncRNA LINC00961. This polypeptide is conserved between human and mouse, is localized to the late endosome/lysosome and interacts… 
View on Nature
ncbi.nlm.nih.gov
338 Citations
Highly Influential Citations
7
Background Citations
72
Methods Citations
6

338 Citations

Citation Type

Citation Type

SPAR, a lncRNA encoded mTORC1 inhibitor
TLDR
A novel polypeptide is uncovered, which is encoded by the lncRNA LINC00961, and regulates amino acid dependent mTORC1 signaling, and is validated by a mass spectrometry based pipeline to identify lnc RNA translated ORFs.
Long Noncoding RNA: Genomics and Relevance to Physiology.
TLDR
Deep sequencing, coupled with analysis of sequence characteristics, is the primary method used to identify lncRNAs, and Identification of nucleic acids or proteins with which an lncRNA interacts is essential for understanding the molecular mechanism underlying its physiological role.
The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function
Abstract Aims Long non-coding RNAs (lncRNAs) play functional roles in physiology and disease, yet understanding of their contribution to endothelial cell (EC) function is incomplete. We identified…
Non-coding RNAs Shaping Muscle
TLDR
The recent findings on the mechanisms used by lncRNAs and circRNAs to sustain skeletal and cardiac muscle formation are discussed, paying particular attention to the technological developments that, over the last few years, have aided their genome-wide identification and study.
Translation of noncoding RNAs and cancer.
TLDR
The aim of this review is to provide a theoretical basis that might promote the discovery of more peptides/proteins encoded by ncRNAs and aid the further development of novel diagnostic and prognostic cancer markers and therapeutic targets.
The Key Lnc (RNA)s in Cardiac and Skeletal Muscle Development, Regeneration, and Disease
TLDR
Key lncRNAs that function as regulators of development, regeneration, and disease in cardiac and skeletal muscle and the contributions of these loci on the regulation of gene expression are highlighted.
An integrative proteogenomics approach reveals peptides encoded by annotated lincRNA in the mouse kidney inner medulla.
TLDR
This work proposes an integrative workflow for lincRNA-encoded peptide discovery and tested it on the mouse kidney inner medulla, discovering three novel lincRNAs, which are conserved in mouse, rat, and human.
The LINC00961 transcript and its encoded micropeptide SPAAR regulate endothelial cell function.
TLDR
The functional importance of a micropeptide-encoding RNA transcript in the vascular endothelium is described and dissected, and it is demonstrated that both the RNA and the peptide regulate endothelial biology.
Long Non-Coding RNAs in Metabolic Organs and Energy Homeostasis
TLDR
This work reviews lncRNAs affecting metabolic organs with a focus on the liver, pancreas, skeletal muscle, cardiac muscle, brain, and adipose organ, and discusses the impact of lnc RNAs on metabolic diseases such as obesity and diabetes.
A ubiquitin-like protein encoded by the "noncoding" RNA TINCR promotes keratinocyte proliferation and wound healing.
TLDR
It is shown that TINCR encodes a ubiquitin-like protein that is well conserved among species and whose expression was confirmed by the generation of mice harboring a FLAG epitope tag sequence in the endogenous open reading frame as well as by targeted proteomics.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 24 REFERENCES
A Micropeptide Encoded by a Putative Long Noncoding RNA Regulates Muscle Performance
TLDR
Findings identify myoregulin (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 noncoding.
A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle
TLDR
Dwarf open reading frame (DWORF) is the only endogenous peptide known to activate the SERCA pump by physical interaction and provides a means for enhancing muscle contractility.
Small Peptides Switch the Transcriptional Activity of Shavenbaby During Drosophila Embryogenesis
TLDR
The results demonstrate that during Drosophila embryogenesis, Pri sORF peptides provide a strict temporal control to the transcriptional program of epidermal morphogenesis.
The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.
TLDR
The most complete human lncRNA annotation to date is presented, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts, and expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes.
Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses.
TLDR
It is found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that l incRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes.
SLC38A9 is a component of the lysosomal amino acid-sensing machinery that controls mTORC1
TLDR
SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR, and is established as an integral part of the Ragulator–RAG GTPases machinery.
Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy.
TLDR
It is demonstrated that muscle mTORC1 has an unexpected role in the regulation of the metabolic properties and that its function is essential for life.
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
TLDR
It is found that the Rag proteins—a family of four related small guanosine triphosphatases (GTPases)—interact with mTORC1 in an amino acid–sensitive manner and are necessary for the activation of the m TORC1 pathway by amino acids.
Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes
TLDR
A suite of techniques, based on ribosome profiling, are presented to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation, revealing an unanticipated complexity to mammalian proteomes.
Conserved Regulation of Cardiac Calcium Uptake by Peptides Encoded in Small Open Reading Frames
TLDR
Two smORF-encoded peptides of less than 30 amino acids regulating calcium transport and, hence, regular heart contraction, in the fruit fly Drosophila heart are described, suggesting that the mechanisms for heart regulation are ancient and that smORFs may be a fundamental genome component that should be studied systematically.
...
1
2
3
...