Evidence map›Paper›PMID 39372743›Full record

ArticlebioRxiv : the preprint server for biology2024

Systemic identification of functionally conserved lncRNA metabolic regulators in human and mouse livers.

Chengfei Jiang, Zhe Li, Ping Li, Yonghe Ma, Sunmi Seok, Stephanie K Podguski, Shria Moturi, Nao Yoneda, Kenji Kawai, Shotaro Uehara and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Chengfei JiangCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Zhe LiCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ping LiCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yonghe MaCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sunmi SeokCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Stephanie K PodguskiCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shria MoturiCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nao YonedaLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
Kenji KawaiPathology Center, Translational Research and Contract Research Service Division, Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
Shotaro UeharaLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
Yasuyuki OhnishiLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
Hiroshi SuemizuLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
Jinwei ZhangLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.ORCID 0000-0002-2114-173X
Haiming CaoCardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Funding

Molecular Basis of Obesity and Obesity-induced Metabolic DiseasesZIAHL006103 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI CAO, HAIMING · 2011 to 2025
$19.8M
Modeling Type II Diabetes and Lipodystrophy Using Patient-Specific iPS CellsZIAHL006159 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI CAO, HAIMING · 2012 to 2025
$14.2M
Intramural NIH HHS ZIA HL006103Intramural NIH HHS ZIA HL006159
6 · The paper itself

Abstract

BACKGROUND &

aimsUnlike protein-coding genes, the majority of human long non-coding 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 non-conserved 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 LMR pairs (h/mLMRs).

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 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-mTOR-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 non-conserved 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 deep phenotyping of genetic mLMR mouse models constitutes a powerful approach to understand the pathophysiological role of lncRNAs in the human liver.

Indexed as

human liverlipid metabolismliver diseaseslncRNA motiflong non-coding RNAs (lncRNAs)

Identifiers

PMID39372743
PMCPMC11451612

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Registered trials

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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.