Evidence mapPaperPMID 40436842Full record

ArticleNature communications2025

An RNA transmethylation pathway governs kidney nephrogenic potential.

Harini Ramalingam, Jesus Alvarez, Andrea Flaten, Patricia Cobo-Stark, Nicholas Foster, Elyse Grilli, Ronak Lakhia, Karam Aboudehen, Thomas Carroll, Vishal Patel

Abstract read
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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Epigenetic regulation of kidney development.Nature reviews. Nephrology · 2026
    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

10 authors.

Harini RamalingamDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID http://orcid.org/0000-0001-7029-9069
Jesus AlvarezDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Andrea FlatenDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Patricia Cobo-StarkDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID http://orcid.org/0000-0002-8113-6211
Nicholas FosterDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Elyse GrilliDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Ronak LakhiaDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID http://orcid.org/0000-0002-4511-5341
Karam AboudehenDepartment of Medicine and Division of Nephrology, Stony Brook University, Stony Brook, NY, USA.
Thomas CarrollDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID http://orcid.org/0000-0002-8322-4928
Vishal PatelDepartment of Internal Medicine and Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA. vishald.patel@utsouthwestern.edu.ORCID http://orcid.org/0000-0003-2875-4659

Funding

The impact of RNA chemical modifications on polycystic kidney disease progressionR01DK102572 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Vishal Patel · 2023 to 2024
$828k
Investigating intracellular cholesterol biosynthesis as a regulator of polycystic kidney disease progressionR01DK139033 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$505k
NIDDK NIH HHS R01 DK080004NIDDK NIH HHS R01 DK090127NIDDK NIH HHS R01 DK095057NIDDK NIH HHS R01 DK102572NIDDK NIH HHS R01 DK139033U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK102572
6 · The paper itself

Abstract

The adult kidney lacks the ability to generate new nephrons, placing individuals born with low nephron counts at greater risk for chronic kidney disease as they age. Limited nutrient availability hinders nephron formation; however, the key metabolic dependencies remain unclear. Here we show that S-adenosylmethionine (SAM) and cellular transmethylation status are crucial determinants of the kidney's nephrogenic capacity. The RNA methyltransferase METTL3 serves as a SAM sensor and is essential for the fate determination of nephron progenitor cells (NPCs). Reducing transmethylation or inhibiting METTL3 blocks NPC differentiation and nephrogenesis, whereas enhancing transmethylation or increasing METTL3 activity facilitates an induced NPC population and increases nephron production. Additionally, we identify Lrpprc mRNA, encoding a mitochondrially enriched protein, as a key direct target of METTL3-mediated transmethylation. Accordingly, inhibiting LRPPRC negates the nephrogenic effects of SAM and METTL3. Our findings reveal a modifiable methionine-SAM-RNA transmethylation pathway that can be targeted to enhance nephron formation.

Indexed as

KidneyMethyltransferasesNephronsRNAAnimalsCell DifferentiationHumansMaleMethylationMiceMice, Inbred C57BLOrganogenesisRNA, MessengerS-AdenosylmethionineStem CellsMethyltransferasesMettl3 protein, mouseRNARNA, MessengerS-Adenosylmethionine

Identifiers

PMID40436842
PMCPMC12120073

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.