RNA-Mediated Non-Mendelian Inheritance in Mice: The Power of Memory

The mouse genome is transcribed at different rates in both directions from the newly formed genome after fertilization. During embryonic genomic activation (EGA/ZGA), the first RNA metabolism creates heterogeneity between blastomeres. Indeed, ZGA-dependent maternal RNA degradation is crucial to regulate gene expression and enable the initiation and acquisition of full developmental competence. Subsequently, from the new genome, in addition to mRNAs, a wide range of regulatory ncRNAs are also transcribed. Regulatory ncRNAs (non-coding RNAs) have profoundly influenced fields ranging from developmental biology to RNA-mediated non-Mendelian inheritance, exhibiting sequence-specific functions. To date, the database cataloging ncRNA is not exhaustive, but their high sequence diversity, length and low expression level can vary within the same genome depending on environmental conditions, making understanding their functions often ambiguous. Indeed, during transcription control, cellular RNA content varies continuously. This phenomenon is observed in genetically identical organisms studied-bacteria, flies, plants and mammals-due to changes in transcription rates, and therefore, it impacts cellular memory. Importantly, experimental data regarding the simple modification of RNAs levels by microinjection into fertilized mouse eggs suggest that they certainly play a driving role in establishing and transmitting newly formed expression information. The idea here is that, even in a stable genome, transcripts can vary rapidly and significantly in response to environmental changes, initiated by transcriptional variations in the genome, thus altering cellular memory.