Evidence map›Paper›PMID 40674449›Full record

ArticleScience (New York, N.Y.)2025

A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.

Guoping Li, Lingfei Sun, Cuiyan Xin, Tian Hao, Prakash Kharel, Aidan C Manning, Christopher L O'Connor, Henry Moore, Shuwen Lei, Priyanka Gokulnath and 26 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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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

36 authors.

Guoping LiCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3874-0744
Lingfei SunCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cuiyan XinDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-5343-8554
Tian HaoDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0009-0007-8657-0424
Prakash KharelDivision of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3886-2311
Aidan C ManningDepartment of Biomolecular Engineering, Baskin School of Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID 0000-0001-9369-6008
Christopher L O'ConnorDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0002-1888-728X
Henry MooreDepartment of Biomolecular Engineering, Baskin School of Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
Shuwen LeiMaterials and Process Simulation Center, California Institute of Technology, Pasadena, CA, USA.ORCID 0000-0003-3828-4742
Priyanka GokulnathCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2813-330X
Xinyu YangDongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.ORCID 0009-0004-1441-1553
Ritin SharmaEarly Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ, USA.ORCID 0000-0001-8365-9916
Krystine Garcia-MansfieldEarly Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ, USA.ORCID 0000-0002-9089-2254
Priyadarshini PanthamDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA.
Chunyang XiaoCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1972-2241
Hanna Y WangCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Emeli ChatterjeeCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4515-1473
Seungbin YimDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0009-0005-9291-5885
Leo B RenDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0009-0002-1238-8009
Michail SpanosCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1205-4201
Hua ZhuDepartment of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.ORCID 0000-0001-7136-7326
Haobo LiDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-5660-7835
Ji LeiPenn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-7704-2370
James F MarkmannPenn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-2762-6535
Louise C LaurentDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-2095-7534
John J RossiRNA Biology and Therapeutics, Beckmann Research Institute, City of Hope, Duarte, CA, USA.
Oluwaseun AkejuDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6740-1250
Quanhu ShengDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0001-8951-9295
Ravi V ShahVanderbilt Translational and Clinical Research Center, Cardiology Division, Vanderbilt University Medical Center, Nashville, TN, USA.
William A GoddardMaterials and Process Simulation Center, California Institute of Technology, Pasadena, CA, USA.ORCID 0000-0003-0097-5716
Todd M LoweDepartment of Biomolecular Engineering, Baskin School of Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
Patrick PirrotteEarly Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ, USA.ORCID 0000-0003-1360-6039
Markus BitzerDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Pavel IvanovDivision of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Joseph V BonventreDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7144-386X
Saumya DasCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4521-4606

Funding

Functional role and therapeutic targeting of exosomes and extracellular RNA biomarkers in heart failureR35HL150807 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Saumya Das · 2020 to 2026
$6.7M
Mechanisms of Ischemic Kidney Injury and RepairR01DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JOSEPH VINCENT BONVENTRE · 1987 to 2026
$6.2M
A Unified Atlas of Dynamic tRNA FunctionR01HG006753 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI LOWE, TODD MICHAEL · 2012 to 2022
$4.6M
tRNA-derived stress-induced RNAs and translational controlR01GM146997 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI IVANOV, PAVEL · 2022 to 2025
$1.6M
Engineering RNA editing tools for the generation of functional tRNA-derived small RNAs in the kidneyR21DK137432 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BONVENTRE, JOSEPH VINCENT, DAS, SAUMYA · 2023 to 2023
$332k
NHGRI NIH HHS R01 HG006753NHLBI NIH HHS R35 HL150807NIDDK NIH HHS R01 DK039773NIDDK NIH HHS R21 DK137432NIGMS NIH HHS R01 GM146997
6 · The paper itself

Abstract

Transfer RNA-derived small RNAs (tsRNAs or tDRs) perform a range of cellular functions. Here, we showed that tRNA-Asp-GTC-3'tDR, a hypoxia-induced tDR derived from the 3' end of tRNA-Asp-GTC, activated autophagic flux in kidney cells and its silencing blocked autophagic flux. Functional gain-/loss-of-function studies in murine kidney disease models demonstrated a substantial renoprotective function of tRNA-Asp-GTC-3'tDR. Mechanistically, tRNA-Asp-GTC-3'tDR assembled stable G-quadruplex structures and sequestered pseudouridine synthase 7 (PUS7), preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directed histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. This tDR-induced RNA autophagy pathway was activated during murine and human kidney diseases, suggesting clinical relevance. Thus, tRNA-Asp-GTC-3'tDR plays a role in regulating RNA autophagy, which helps to maintain homeostasis in kidney cells and protects against kidney injury.

Indexed as

AutophagyKidneyRNA, Small UntranslatedAnimalsCell HypoxiaHumansMaleMiceMice, Inbred C57BLPseudouridineRNA, MessengerRNA, TransferPseudouridineRNA, MessengerRNA, Small UntranslatedRNA, Transfer

Identifiers

PMID40674449
PMCPMC12967313

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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.