Bioinformatic analysis revealing association of exosomal mRNAs and proteins in epigenetic inheritance

Transgenerational inheritance of environment induced phenotype requires transmission of epigenetic information through the germline. Whereas several epigenetic factors have been implicated in germline transmission, mediators of information transfer from soma to the germline remain unidentified in mammals. Notably, a recent bioinformatic analysis showed association of extracellular microRNAs (miRNAs) and altered transcriptomes in diverse instances of mammalian epigenetic inheritance involving different environmental factors, tissues, life cycle stages, generations and genders. It was predicted that regulatory non-coding RNAs (ncRNAs) may potentially mediate soma to germline information transfer. Remarkably, the present bioinformatic evidence suggests similar association of exosomal mRNAs and proteins. The differentially expressed genes reported previously in genome level expression profiling studies related to or relevant in epigenetic inheritance showed enrichment for documented set of exosomal mRNAs in a few instances of epigenetic inheritance and of exosomal proteins in a majority of instances. Differentially expressed genes encoding exosomal miRNAs and proteins, directly or indirectly through first and/or second degree interactome networks, overrepresented biological processes related to environmental factors used in these instances as well as to epigenetic alterations, especially chromatin and histone modifications. These findings predict that exosomal mRNAs and proteins, like extracellular miRNAs, may also potentially mediate soma to germline information transfer. A convergent conceptual model is presented wherein extracellular ncRNAs/miRNA, mRNAs and proteins provide the much needed continuum inclusive of epigenetic inheritance. The phrase “transgenerational systems biology” is introduced to signify that the realm of systems biology extends beyond an individual organism and encompasses generations.