Non-coding RNAs as direct and indirect modulators of epigenetic regulation

Abstract

Epigenetic regulation of gene expression is an increasingly well-understood concept that explains much of the contribution of an organism's environment and experience to its biology. However, discussion persists as to which mechanisms can be classified as epigenetic. Ongoing research continues to uncover novel pathways, including the important role of non-protein coding RNA transcripts in epigenetic gene regulation. We know that the majority of human and other mammalian transcripts are not translated but that many of these are nonetheless functional. These non-coding RNAs (ncRNAs) can be short (<200 nt) or long (<200 nt) and are further classified by genomic origin and mechanism of action. We discuss examples of ncRNAs that interact with histone modifying complexes or DNA methyltransferases to regulate gene expression, others that are targets of these epigenetic mechanisms, and propose a model in which such transcripts feed back into an epigenetic regulatory network.

Keywords: chromatin; epigenetics; gene expression; histone; lncRNA; microRNA; noncoding RNA; piRNA; polycomb.

Figure 1. Environmentally sensitive, dynamic regulation of gene expression by long and short ncRNAs occurs through direct and indirect interaction with classical epigenetic mechanisms, forming a larger epigenetic network. ncRNAs are known to bind and recruit histone modifying complexes to either add (A) or remove (B) methyl and acetyl groups. These transcripts also modulate DNA methyltransferases (C), thereby facilitating or suppressing DNA methylation. Loci that are targeted by each of these mechanisms can encode protein coding and/or noncoding RNA transcripts (D). ncRNAs in turn can affect gene expression by interacting with mRNA, or through feedback into the previously discussed pathways (E).