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lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Cell Type-specific Gene Expression Profiling in the Mouse Liver
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Systemic Identification of Functionally Conserved Long Noncoding RNA Metabolic Regulators in Human and Mouse Livers.

Chengfei Jiang1, Zhe Li1, Sunmi Seok1

  • 1Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Gastroenterology
|March 24, 2025
PubMed
Summary

Functionally conserved long noncoding RNA metabolic regulators (fcLMRs) were identified, demonstrating shared liver functions between human and mouse noncoding RNAs. A specific fcLMR, h/mLMR1, regulates triglyceride levels by interacting with PABPC1, offering a potential therapeutic target for hepatic steatosis.

Keywords:
Human LiverLipid MetabolismLiver DiseasesLong non-coding RNAs (lncRNAs)lncRNA Motif

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Area of Science:

  • Genomics
  • Molecular Biology
  • Biochemistry

Background:

  • Most human long noncoding RNAs (lncRNAs) lack sequence conservation, complicating functional studies and clinical translation.
  • This study investigates the hypothesis that nonconserved lncRNAs can share conserved metabolic functions across species, termed functionally conserved lncRNA metabolic regulators (fcLMRs).

Purpose of the Study:

  • To identify and characterize fcLMRs between human and mouse livers.
  • To elucidate the molecular mechanisms by which fcLMRs regulate gene expression and metabolic processes.
  • To explore the therapeutic potential of nonconserved lncRNAs in liver diseases like hepatic steatosis.

Main Methods:

  • Developed a sequence-independent strategy to identify putative fcLMRs.
  • Performed comparative functional analysis of human and mouse lncRNA pairs (h/mLMRs).
  • Investigated the mechanism of action for a specific fcLMR (h/mLMR1) involving PABPC1 interaction and downstream signaling pathways.

Main Results:

  • Identified several putative fcLMRs exhibiting similar gene regulatory functions.
  • Demonstrated that h/mLMR1 regulates triglyceride levels and lipogenic gene expression in both species.
  • Elucidated that h/mLMR1 binds to PABPC1 via structurally similar motifs, inhibiting translation and activating the amino acid-mTOR-SREBP1c pathway.
  • Showed that PABPC1-binding motifs fully rescued lncRNA function across species.
  • Observed elevated h/mLMR1 expression in hepatic steatosis models.

Conclusions:

  • Functionally conserved lncRNA metabolic regulators (fcLMRs) represent a novel and widespread biological phenomenon.
  • Mouse models of lncRNA function are valuable for studying human liver pathophysiology.
  • The PABPC1-binding motif of hLMR1 is a potential drug target for nonconserved lncRNA-mediated diseases like hepatic steatosis.