Abstract
Since the discovery of eukaryotic small RNAs as the main effectors of RNA interference in the late 1990s, diverse types of endogenous small RNAs have been characterized, most notably microRNAs, small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs). These small RNAs associate with Argonaute proteins and, through sequence-specific gene regulation, affect almost every major biological process. Intriguing features of small RNAs, such as their mechanisms of amplification, rapid evolution and non-cell-autonomous function, bestow upon them the capacity to function as agents of intercellular communications in development, reproduction and immunity, and even in transgenerational inheritance. Although there are many types of extracellular small RNAs, and despite decades of research, the capacity of these molecules to transmit signals between cells and between organisms is still highly controversial. In this Review, we discuss evidence from different plants and animals that small RNAs can act in a non-cell-autonomous manner and even exchange information between species. We also discuss mechanistic insights into small RNA communications, such as the nature of the mobile agents, small RNA signal amplification during transit, signal perception and small RNA activity at the destination.
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Acknowledgements
The authors are grateful to N. Alon for help with the illustrations. Research on small RNAs in the Chen laboratory is funded by the US National Institutes of Health (GM129373). The Rechavi laboratory is funded by ERC grant no. 819151.
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Glossary
- Post-transcriptional gene silencing
-
Silencing of genetic elements usually through RNA degradation or the inhibition of their translation.
- Non-cell-autonomous RNA-mediated gene silencing
-
RNA-mediated gene silencing in which the trigger for silencing is delivered to, or originates from, cells that are different from those that undergo gene silencing.
- Symplasm
-
The ‘shared’ cytoplasm of nearly all plant cells due to the presence of the plasmodesmata connecting adjacent plant cells.
- Apoplasm
-
The extracellular (outside the plasma membrane) environment consisting of the cell wall and other molecules therein.
- Phloem
-
A tissue in the plant vasculature that transmits nutrients and other molecules to distant plant parts.
- siRNA–siRNA* duplexes
-
Also miRNA–miRNA* duplexes, products of RNA processing by Dicer, consisting of a duplex of small RNAs with an overhang on each strand. The strand that is not loaded into an Argonaute protein is marked with an asterisk.
- siRNA bodies
-
In Arabidopsis thaliana, cytoplasmic foci containing factors involved in the production of endogenous siRNAs, such as ARGONAUTE 7 (AGO7), SUPPRESSOR OF GENE SILENCING 3 (SGS3) and RNA-DEPENDENT RNA POLYMERASE 6 (RDR6).
- Apoplastic fluid
-
The fluid in the plant apoplasm that can be collected through centrifugation.
- Transcriptional gene silencing
-
Silencing of genetic elements at the transcriptional level, usually through the deposition of repressive histone modifications or DNA methylation.
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Chen, X., Rechavi, O. Plant and animal small RNA communications between cells and organisms. Nat Rev Mol Cell Biol 23, 185–203 (2022). https://doi.org/10.1038/s41580-021-00425-y
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DOI: https://doi.org/10.1038/s41580-021-00425-y
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