mGem: Guides or triggers? Extracellular RNAs beyond vesicular miRNAs

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The field of extracellular RNA (exRNA) biology has expanded significantly.
• Current research often assumes extracellular vesicles (EVs) are the primary carriers of RNA between cells.
• MicroRNAs (miRNAs) are frequently presumed to be the main RNA cargo within EVs.

Purpose of the Study:

• To critically examine prevailing assumptions in exRNA research.
• To highlight overlooked aspects of exRNA biology, particularly concerning EV-miRNA interactions.
• To explore alternative mechanisms and considerations for intercellular RNA communication.

Main Methods:

• Review and critical analysis of existing data and assumptions in exRNA research.
• Examination of the biological requirements for miRNA activity, including cellular localization and endosomal escape.
• Consideration of the quantities of intercellularly transferred miRNAs necessary for biological function.

Main Results:

• Data from mammals to microbes challenge the assumption that EVs are the sole or main carriers of exRNAs.
• The role of miRNAs as the predominant EV RNA cargo is questioned.
• Potential mechanistic challenges for miRNA function, such as endosomal escape and required cellular concentrations, are highlighted.

Conclusions:

• The field of exRNA biology may benefit from questioning established paradigms regarding EV-miRNA communication.
• Further investigation into overlooked aspects of exRNA trafficking and function is warranted.
• A deeper understanding of exRNA biology can provide crucial insights into cellular and organismal interactions.