Tunneling Nanotube-Mediated Communication: A Mechanism of Intercellular Nucleic Acid Transfer

Abstract

Tunneling nanotubes (TNTs) are thin, F-actin-based membranous protrusions that connect distant cells and can provide e a novel mechanism for intercellular communication. By establishing cytoplasmic continuity between interconnected cells, TNTs enable the bidirectional transfer of nuclear and cytoplasmic cargo, including organelles, nucleic acids, drugs, and pathogenic molecules. TNT-mediated nucleic acid transfer provides a unique opportunity for donor cells to directly alter the genome, transcriptome, and metabolome of recipient cells. TNTs have been reported to transport DNA, mitochondrial DNA, mRNA, viral RNA, and non-coding RNAs, such as miRNA and siRNA. This mechanism of transfer is observed in physiological as well as pathological conditions, and has been implicated in the progression of disease. Herein, we provide a concise overview of TNTs’ structure, mechanisms of biogenesis, and the functional effects of TNT-mediated intercellular transfer of nucleic acid cargo. Furthermore, we highlight the potential translational applications of TNT-mediated nucleic acid transfer in cancer, immunity, and neurological diseases.

Human neural stem cells derived from fetal human brain communicate each other and rescue ischemic neurons through tunneling nanotubes

“…Considering that TNTs can transfer RNAs (73) and probably RNA-regulating factors, the TNTs-mediated crosstalk between healthy hNSCs and injured neurons observed here could play a role in coordinating the transcriptomic modi cation of both cell types.…”

Adopted neoplastic cells and the consequences of their existence

“…For example, the activity responsible for the ability of cytoplasts from tumorigenic cells to immortalize human lymphocytes [104] was identified as two short species of endogenous cytoplasmic DNA [160]. Cytoplasmic DNA includes retrotransposons, linear and circular chromatin fragments of various size, mitochondrial DNA, and micronuclei [161], all of which are transferrable by anastomosis [162] or by extracellular vesicles [163][164][165].…”

Targeting CAM-DR and Mitochondrial Transfer for the Treatment of Multiple Myeloma

“…TNTs are filamentous, F-actin-rich, long tubular extensions connecting the cytoplasm of adjacent and/or distant cells that mediate cell-to-cell communication [ 80 , 81 , 82 ]. TNTs are increasingly considered the primary intercellular pathway for the unidirectional and bidirectional movement of nuclear and cytoplasmic cargo, such as nucleic acids, drugs, pathogenic molecules, and organelles, including mitochondria [ 50 , 83 ]. Hypoxic conditions associated with the TME reportedly stimulate an increase in TNT formation [ 84 ].…”