ArticleNature2017
mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 361 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
361 citing papers in PubMed, 630 citations in OpenAlex.
- Functions of exosome-derived noncoding RNA-encoded polypeptides/proteins in human diseases.Genes & diseases · 2027Review
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- The mechanisms of lncBMP4 mediating BMP4 promoter activity to regulate the proliferation of dermal papilla cells in Hu sheep.Animal bioscience · 2026Article
- Microproteins as a Hidden Player in Breast Cancer: From Molecular Insights to Therapeutic Potential.Cell biochemistry and function · 2026Review
- The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides.The EMBO journal · 2026Review
- Essential lncRNAs in the human transcriptome.Cell genomics · 2026Article
- A microprotein encoded by FERMT3 modulates endothelial cell protein catabolism and induces cell cycle arrest and senescence.Cell communication and signaling : CCS · 2026Article
- Integrative analysis of RNA-seq and Ribo-seq reveals that lncRNA regulates chicken myogenesis through encoding peptide.Journal of animal science and biotechnology · 2026Article
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- Computational identification and characterization of noncoding RNA-encoded peptides: tools, databases, and in silico strategies.Amino acids · 2026Review
- Integrated peptidogenomics decoding yak non-conventional peptides: functional mapping and biopotential mining of genetic resources.Animal bioscience · 2026Article
- An Artificial Antibody-Based Toolbox Accelerates Validation of Hidden Microproteins Encoded by the Dark Genome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Retinoic Acid and Long Noncoding RNAs Crosstalk: Implications for Neuronal Differentiation and Diseases.Molecular neurobiology · 2026Review
- The hidden players: LncRNA-Encoded micropeptides in cancer hallmarks.Cellular and molecular life sciences : CMLS · 2026Review
- cncFinder: A graph-attention-network-based interpretable learning model to identify bifunctional long non-coding RNAs.Molecular therapy. Nucleic acids · 2026Article
- Revisiting noncoding RNAs: emerging coding functions and their impact on skeletal muscle development.Experimental & molecular medicine · 2026Review
- LncRNA Knockdown Using Gapmer Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2026Article
- RNA variation as the driver of genomic efficiency and phenotypic complexity.International journal of biological sciences · 2026Review
- TPT: a compact CNN-transformer encoder for efficient microbial small protein modeling.Frontiers in microbiology · 2026Article
301 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
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 with the lysosomal v-ATPase to negatively regulate mTORC1 activation. This regulation of mTORC1 is specific to activation of mTORC1 by amino acid stimulation, rather than by growth factors. Hence, we termed this polypeptide 'small regulatory polypeptide of amino acid response' (SPAR). We show that the SPAR-encoding lncRNA is highly expressed in a subset of tissues and use CRISPR/Cas9 engineering to develop a SPAR-polypeptide-specific knockout mouse while maintaining expression of the host lncRNA. We find that the SPAR-encoding lncRNA is downregulated in skeletal muscle upon acute injury, and using this in vivo model we establish that SPAR downregulation enables efficient activation of mTORC1 and promotes muscle regeneration. Our data provide a mechanism by which mTORC1 activation may be finely regulated in a tissue-specific manner in response to injury, and a paradigm by which lncRNAs encoding small polypeptides can modulate general biological pathways and processes to facilitate tissue-specific requirements, consistent with their restricted and highly regulated expression profile.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.