In a paradigm shift for RNA biology, thanks to the discovery and characterization of extracellular RNA (exRNA), it is now known that RNA plays an important role in cell-to-cell communication. Several groups have reported on the different roles that exRNA communication plays in fertilization. In a recent study using low-bias RealSeq-AC libraries to profile ncRNAs from extracellular vesicles (EVs), Reshi and collaborators reported that spermatozoa alter the cargo of extracellular vesicles from oviductal cells. This study further demonstrates the power of accurate exRNA profiling to further study RNA communication.
This study also dissects the RNA cross-talk between oviduct and spermatozoa. The experiments reported use a method that allows the collection of EVs generated upon direct contact and non-contact interaction of spermatozoa with oviductal cells. Using RealSeq-AC libraries to profile ncRNAs from low-yield RNA preps of isolated EVs, the authors further identified distinct cargo for EVs generated by direct vs non-direct spermatozoa contact. Interestingly, mRNA fragments included as EVs cargo, also varied within the different groups with a high proportion of the RNA comprising intron-derived transcripts. This highlights the importance of profiling RNA fragments to identify changes in cellular transcriptome. Additionally, as stated by the authors when talking about RNA fragments with no known function: “Such material, even if it has no functional role in recipient cells, may therefore comprise a rich pool of biomarkers.”
The main conclusion from the study is that the oviduct is not merely a passageway for spermatozoa but a dynamic organ, where RNA cross-talk between spermatozoa and oviductal epithelial cells plays an important role. The RealSeq-AC technology facilitated this novel finding by allowing the accurate profiling of exRNAs from low input samples.