Evidence map›Paper›PMID 41398161›Full record

ArticleNature communications2025

A cholesterol-responsive hepatic tRNA-derived small RNA regulates cholesterol homeostasis and atherosclerosis development.

Xiuchun Li, Rebecca Hernandez, Xudong Zhang, Sijie Tang, Xiaohong Yuan, Jing Wu, Kathy Pham, Hukam C Rawal, Erica C Heinrich, Shenglong Zhang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Xiuchun LiDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
Rebecca HernandezDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.ORCID http://orcid.org/0000-0003-4127-3323
Xudong ZhangMolecular Medicine Program, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-5964-0067
Sijie TangDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.ORCID http://orcid.org/0000-0001-6588-1855
Xiaohong YuanDepartment of Biological and Chemical Sciences, New York Institute of Technology, New York, NY, USA.ORCID http://orcid.org/0000-0002-9165-5197
Jing WuDepartment of Biological and Chemical Sciences, New York Institute of Technology, New York, NY, USA.
Kathy PhamDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
Hukam C RawalDepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.ORCID http://orcid.org/0000-0002-2727-9721
Erica C HeinrichDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.ORCID http://orcid.org/0000-0002-6861-6165
Shenglong ZhangDepartment of Biological and Chemical Sciences, New York Institute of Technology, New York, NY, USA.ORCID http://orcid.org/0000-0001-8003-7484
Qi ChenMolecular Medicine Program, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0001-6353-9589
Tong ZhouDepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.ORCID http://orcid.org/0000-0003-2361-1931
Changcheng ZhouDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA. changcheng.zhou@ucr.edu.ORCID http://orcid.org/0000-0001-7649-0710

Funding

Sperm tsRNAs/rsRNAs and their RNA modifications in diet-induced epigenetic inheritanceR01HD092431 · NICHD · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Qi Chen, David S Milstone · 2017 to 2026
$3.5M
Role of PXR in EDC-induced cardiovascular diseaseR35ES035015 · NIEHS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Changcheng Zhou · 2023 to 2026
$3.4M
Role of PXR in drug-elicited cardiovascular diseaseR01HL167206 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Hong Chen, Changcheng Zhou · 2023 to 2026
$2.8M
Development of Next-Generation Mass Spectrometry-based de novo RNA Sequencing for all ModificationsR01HG012853 · NHGRI · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI Shenglong Zhang · 2023 to 2026
$2.6M
Decoding the signature of sperm RNA & RNA modification of environmental stressors on the intergenerational transmission of metabolic phenotypesR01ES032024 · NIEHS · UNIVERSITY OF UTAH · PI CHEN, QI, ZHOU, TONG · 2020 to 2024
$2.1M
NHGRI NIH HHS R01 HG012853NHLBI NIH HHS R01 HL167206NICHD NIH HHS R01 HD092431NIEHS NIH HHS R01 ES032024NIEHS NIH HHS R35 ES035015U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01ES032024U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HD092431U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HG012853U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HL167206U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35ES035015
6 · The paper itself

Abstract

Transfer RNA-derived small RNAs (tsRNAs) have emerged as crucial players in diverse biological processes. Yet, their involvement in lipid metabolism and cardiovascular disease remains elusive. Using an advanced PANDORA-seq method, we identify tsRNA-Glu-CTC as the most abundant tsRNA in mouse liver. Intriguingly, tsRNA-Glu-CTC is cholesterol responsive. Overexpression of tsRNA-Glu-CTC elicits hypercholesterolemia and hepatic steatosis, whereas its knockdown protects against diet-induced hypercholesterolemia and atherosclerosis in mice. Mechanistically, tsRNA-Glu-CTC regulates key hepatic lipogenic genes including Srebp2, a master regulator of lipid metabolism. tsRNA-Glu-CTC interacts with SREBP2 to regulate its own transcription through an E-box motif. We further identify site-specific RNA modifications of endogenous tsRNA-Glu-CTC by a mass spectrometry-based MLC-seq and demonstrate the modified tsRNA-Glu-CTC as a more potent regulator of cholesterol homeostasis compared to its unmodified synthetic counterpart. Collectively, our study reveals an important role of a liver-enriched tsRNA in lipid metabolism and cardiovascular health, opening new therapeutic avenues for cardiometabolic disease.

Indexed as

AtherosclerosisCholesterolLiverRNA, TransferAnimalsFatty LiverHomeostasisHumansHypercholesterolemiaLipid MetabolismMaleMiceMice, Inbred C57BLSterol Regulatory Element Binding Protein 2CholesterolRNA, TransferSrebf2 protein, mouseSterol Regulatory Element Binding Protein 2

Identifiers

PMID41398161
PMCPMC12706008

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.