Non-coding RNAs: the architects of eukaryotic complexity - PubMed (original) (raw)

Non-coding RNAs: the architects of eukaryotic complexity

J S Mattick. EMBO Rep. 2001 Nov.

Abstract

Around 98% of all transcriptional output in humans is non-coding RNA. RNA-mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like RNA interference, co-suppression, transgene silencing, imprinting, methylation, and possibly position-effect variegation and transvection, all involve intersecting pathways based on or connected to RNA signaling. I suggest that the central dogma is incomplete, and that intronic and other non-coding RNAs have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system of trans-acting RNAs that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, RNA-DNA, RNA-RNA and RNA-protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing.

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Figures

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Fig. 1. Comparison of the prokaryotic and proposed eukaryotic genetic operating systems. The left panel shows the central dogma in which genes code, via mRNA, for proteins, which carry out the catalytic, structural, signal transduction and regulatory functions of the cell. The right panel shows the proposed operating system in eukaryotes wherein genes may express two levels of information: mRNA for proteins, and eRNAs that carry out concomitant networking and other functions within the organism. Thus there are three types of genes in eukaryotes: those that encode only protein (which are rare), those that encode only eRNA, and those that encode both.

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Fig. 2. A more detailed schematic of the proposed role of eRNAs in eukaryotic system networking and control. Genes, packaged in chromatin, express primary transcripts which are then (alternatively) spliced to yield an mRNA and/or n introns, which may be further processed to form multiple smaller species, such as let-7. Some noncoding RNA genes may yield functional RNAs from both introns and exons (nRNA). These RNAs may then act as signaling or guide molecules to integrate activity at this locus with that of related parts of the network, via effects on chromatin structure, transcription, splicing, other levels of RNA processing, mRNA translation, mRNA stability and other levels of RNA-mediated signal transduction within the cell. The evidence indicates that many if not most of these interactions will be homology (primary sequence) dependent, and involve RNA–DNA, RNA–RNA and RNA–protein interactions, but others may involve secondary or tertiary RNA structures and RNA-mediated catalysis. This scheme is not comprehensive, but is intended to give a sense of the complexity and potential of such networks for programmed control and system integration of complex suites of gene activity in differentiation and development.

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John S. Mattick

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