Affiliation:
1. Department of Molecular Genetics, Weizmann Institute of Science
2. Berlin Institute of Medical Systems Biology and Systems Biology, Max Delbruck Center for Molecular Medicine
3. Department of Anatomy & Structural Biology, Albert Einstein College of Medicine
Abstract
Full-length mRNAs transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (the ‘transferome’) is unknown. Here, we analyzed the transferome in an in vitro human-mouse cell co-culture model using RNA-sequencing. We found that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells. Typically,<1% of endogenous mRNAs undergo transfer. Non-selective, expression-dependent RNA transfer was further validated using synthetic reporters. RNA transfer appears contact-dependent via TNTs, as exemplified for several mRNAs. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions.
Funder
German-Israeli Foundation for Scientific Research and Development
US-Israel Binational Science Foundation-National Science Foundation
Joel and Mady Dukler Fund for Cancer Research
Jean-Jacques Brunschwig Fund for the Molecular Genetics of Cancer
Moross Integrated Cancer Center
Kekst Family Institute for Medical Genetics
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
4 articles.
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