ArticleGastroenterology2025
Systemic Identification of Functionally Conserved Long Noncoding RNA Metabolic Regulators in Human and Mouse Livers.
Article in Gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed.
- PABPC1 in Cancer: From a Translational Housekeeper to a Stress-Responsive Regulatory Hub.Cancer science · 2026Review
- Beyond Junk DNA: Emerging Roles of Non-Coding RNAs in Cancer and Therapeutic Innovation.Biomolecules · 2026Review
- Comparative transcriptome analysis of Qinchuan and Wagyu cattle reveals lnc11599 as a negative regulator of intramuscular fat deposition.BMC genomics · 2026Article
- TheNon-coding RNA · 2025Article
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14 authors.
Funding
Abstract
BACKGROUND &
aimsUnlike protein-coding genes, most human long noncoding RNAs (lncRNAs) lack conservation based on their sequences, posing a challenge for investigating their role in a pathophysiological context for clinical translation. This study explores the hypothesis that nonconserved lncRNAs in human and mouse livers may share similar metabolic functions, giving rise to functionally conserved lncRNA metabolic regulators (fcLMRs).
methodsWe developed a sequence-independent strategy to select putative fcLMRs and performed extensive analysis to determine the functional similarities of putative human and mouse (h/m)LMR pairs.
resultsWe found that several pairs of putative fcLMRs share similar functions in regulating gene expression. We further demonstrated that a pair of fcLMRs, h/mLMR1, robustly regulated triglyceride levels by modulating the expression of a similar set of lipogenic genes. Mechanistically, h/mLMR1 binds to poly(A)-binding protein cytoplasmic 1 (PABPC1), a regulator of protein translation, via short motifs on either lncRNA with divergent sequences but similar structures. This interaction inhibits protein translation, activating an amino acid- mechanistic target of rapamycin (mTOR)-sterol regulatory element-binding transcription factor 1 (SREBP1) axis to regulate lipogenic gene expression. Intriguingly, PABPC1-binding motifs on each lncRNA fully rescued the functions of their corresponding LMRs in the opposite species. Given the elevated expression of h/mLMR1 in humans and mice with hepatic steatosis, the PABPC1-binding motif on hLMR1 emerges as a potential nonconserved human drug target whose functions can be fully validated in a physiologically relevant setting before clinical studies.
conclusionsOur study supports that fcLMRs represent a novel and prevalent biological phenomenon and that deep phenotyping of genetic mLMR mouse models constitutes a powerful approach to understand the pathophysiological role of lncRNAs in the human liver.
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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.