SLAMseq reveals potential transfer of RNA from liver to kidney in the mouse

Extracellular RNA (exRNA) mediates intercellular communication in lower animals; whether it serves a signalling function in mammals is uncertain. Reductionist experiments, in which a single RNA is over-expressed or tagged, have shown RNA transfer between tissues but may not be relevant to normal phy...

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Bibliographic Details
Published in:Nature communications Vol. 16; no. 1; pp. 7413 - 14
Main Authors: Hunter, Robert W., Sun, Jialin, Palmer, Trecia, Czopek, Alicja, Nespoux, Josselin, Bailey, Matthew A., Dhaun, Neeraj, Buck, Amy H., Dear, James W.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 11.08.2025
Nature Publishing Group
Nature Portfolio
Subjects:
45/71
45/91
631/337
692/4022
Alkylation
Analgesics
Animals
Cell interactions
Conversion
Experiments
Gene sequencing
Genes
Hepatocytes
Hepatocytes - metabolism
Humanities and Social Sciences
Hypotheses
Incorporation
Injury prevention
Kidney - metabolism
Kidneys
Kruskal-Wallis test
Labeling
Labels
Liver
Liver - metabolism
Male
Metabolism
Mice
Mice, Inbred C57BL
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
multidisciplinary
Physiology
Ribonucleic acid
RNA
RNA - metabolism
RNA Transport
RNA, Messenger - genetics
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
Sequence Analysis, RNA - methods
Spleen
Thiouracil - chemistry
Thiouracil - metabolism
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Extracellular RNA (exRNA) mediates intercellular communication in lower animals; whether it serves a signalling function in mammals is uncertain. Reductionist experiments, in which a single RNA is over-expressed or tagged, have shown RNA transfer between tissues but may not be relevant to normal physiology. Here, we seek to determine the scale of RNA transfer between liver and kidney using metabolic RNA labelling in mice. We use 4-thiouracil to label RNA in hepatocytes and then detect labelled RNA in the kidney using SLAMseq: SH-Linked Alkylation for Metabolic RNA sequencing. We show that in the kidney, 5% of mRNA transcripts are labelled in health, increasing to 34% after acute hepatocellular injury. In the kidney, we do not detect labelled small RNA, but do find higher levels of the liver-enriched miRNA, miR-122 after liver injury. Our results show potential transfer of RNA from liver to kidney: a phenomenon that is augmented by liver injury. There were important limitations: we could not confidently identify transferred RNA transcripts at the single-gene level and we did not assess the physiological consequences of any RNA transfer. Hunter et al. use RNA labelling to investigate RNA transfer between organs in mice. They show that RNA potentially moves en masse from liver to kidney and that this movement is augmented in acute liver injury, although the physiological relevance of the phenomenon is not yet known.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-025-62688-9