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Our opinion article on #exRNA release mechanisms and their impact on intercellular communication is now online in @TrendsBiochem. You can read it here: https://www.sciencedirect.com/science/article/pii/S0968000420303169?dgcid=author (1/8)
We tend to think in intercellular communication in classical terms: communication needs a message sent from one emisor to one specific receptor, right? If RNA is the message, the cell needs a selective packaging system to ensure that only the right RNAs are sent...
Here, we explored a "social media-based communication" model where a cell releases a representative fraction of its transcriptome to the extracellular space. Instead of communicating one specific message to a specific target cell, it communicates "itself" to its "followers"
Mechanisms used by cells to release RNAs into the extracellular space do not necessarily determine exRNA functionality. Interest in selectively-released exRNAs is obviously justified, but nonselective RNA sorting into the extracellular space could be functionally relevant as well
Emphasis on selective sorting mechanisms has downplayed the importance of those RNAs that are highly abundant both inside and outside cells, simply because they do not show extracellular enrichment. However, they might be better positioned to induce a response in recipient cells
Exocytosis was once thought to be a way cells released their garbage into the extracellular space. Then, extracellular RNAs were shown to play a role in intercellular communication. So, they started to be considered gold rather than trash. But they can be simultaneously both!
Another interesting aspect of this perspective is that dead cells might be active players in RNA-mediated intercellular communication, especially when the receptors are immune cells 
This work was inspired by recent reports on extracellular processing of nonvesicular exRNAs by our group & the lab of Thomas Gingeras at @CSHL. Great collaboration with @KennethWWitwer as part of the NIH #ERCC2 @exRNA. Thanks also to @ANIIuy @PEDECIBA @IPMontevideo and @Udelaruy
