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. Author manuscript; available in PMC: 2023 Mar 1.
Published in final edited form as: Nat Rev Mol Cell Biol. 2021 Oct 27;23(3):185–203. doi: 10.1038/s41580-021-00425-y

Fig. 3 ∣. Cell-to-cell and long-distance transfer of small RNAs.

Fig. 3 ∣

a ∣ The cytoplasm of plant cells is connected through plasmodesmata to form the symplasm (white space in the figure), which allows the exchange of nutrients and biomolecules, including small RNAs. Sieve element (SE) cells in the phloem are connected by pores and mediate long-distance transfer of molecules. Companion cells (CCs) are connected to sieve elements through branched plasmodesmata and load mobile molecules into the sieve elements. Phloem unloading can occur through different types of cells connected to the sieve elements, depending on the cargo molecules. Phloem pole pericycle (PPP) cells are connected to sieve elements through funnel-shaped plasmodesmata and have been shown to unload proteins. How small RNAs are unloaded from phloem is unknown. Small RNAs are thought to move from cell to cell in the form of duplexes. In Arabidopsis thaliana, ARGONAUTE 1 (AGO1) is cell autonomous and consumes mobile small RNAs as they are transported from cell to cell. b ∣ In Caenorhabditis elegans, the identity of the small RNA agents that move between cells is still unknown. With regard to exogenously induced RNA interference responses, it appears that long double-stranded RNA (dsRNA) or double-stranded small interfering RNAs (siRNAs) — but not single-stranded siRNAs — can move between cells. Direct evidence for shuttling of endogenous small RNAs between cells is missing; however, manipulation of endogenous small RNAs in one tissue (neurons or gut) has non-cell-autonomous effects. Different mobile small RNAs might be secreted from cells or might move to contacting cells that are connected by membrane bridges. The small RNAs might be present in vesicles that bud out of the plasma membrane or might be contained in intraluminal vesicles that fuse with the plasma membrane. It is also possible that mobile small RNAs are released when bound by RNA-binding proteins, such as Argonaute proteins. Although not much is known about export of small RNA out of cells in worms (for example, is the RNA secreted inside microvesicles?), import involves receptors that shuttle the small RNA into the host cell. Transporters (perhaps SID-1) likely release the imported RNA from endocytosis vesicles (specialized endosomes). The imported siRNAs can then direct siRNA amplification and gene silencing.