The ribonome: a dominant force in co-ordinating gene expression

Abstract

The ribonome is the total cellular complement of RNAs and their regulatory factors functioning dynamically in time and space within ribonucleoprotein complexes. We theorize that the ribonome is an ancient central co-ordinator that has evolved to communicate on multiple levels to the proteome on the one hand (feed-forward), and the transcriptome and RNA processing machinery on the other (feed-back). Furthermore, the ribonome can potentially communicate to other cells horizontally with implications for biological information transfer and for the evolution of both RNA and DNA operating systems. The post-transcriptional RNA operon theory of co-regulated gene expression accounts for the co-ordinated dynamics of RNA-binding proteins within the cellular ribonome, thus allowing for the recombination and remodelling of the RNPs (ribonucleoproteins) to generate new combinations of functionally related proteins. Thus, post-transcriptional RNA operons form the core of the ribonomic operating system in which both their control and co-ordination govern outcomes. Within the ribonome, RNA-binding proteins control one another's mRNAs to keep the global mRNA environment in balance. We argue that these post-transcriptional ribonomic systems provide an information management and distribution centre for evolutionary expansion of multicellularity in tissues, organs, organisms, and their communities.

Figure 1. Visualization of the analysis of RNPs within the ribonome

The organization and co-ordination of RNPs that drive post-transcriptional gene expression within the ribonome as experimentally determined using RIP-Chip to detect mRNA and microRNA components of RNP complexes. The finding that functionally related mRNAs are associated with specific RBPs within mRNPs led to the post-transcriptional RNA operon/regulon model of co-ordinated gene expression. Subsequently, other studies using polysome gradient profiling, RNA stability-microarrays and high throughput deep sequencing demonstrated that subsets of functionally related mRNAs can be co-ordinated at the levels of translation and stability (reviewed in Keene, 2007a). Reproduced from Keene (2001) with permission. © (2001) Proc. Natl. Acad. Sci. U.S.A.

Figure 2. Diagram of the RNA processing steps between transcription and translation showing the feedback from translation to each step in the pathway

The flow of both informational mRNAs and regulatory micro-RNAs from transcription and through splicing, export, stability, localization and translation is depicted. The dominance of translation in feeding back and co-ordinating events upstream of the informational flow of mRNA is depicted by green arrows. The combinatorial regulation of translation by RBPs and mi-croRNAs is directed from within RNPs.

Figure 3. RBPs functioning as regulators of regulators

Model of RBPs forming a sub-network in the cytoplasm where they directly regulate the stability or translation of one another’s mRNAs as an interaction balance co-ordination system (Mesarovic et al., 2004). This system is not closed but open to co-ordinating subsets of global mRNA targets (Venn ovals) dynamically in response to incoming signals as determined by the balanced regulation of each RBP in the sub-network.

Figure 4. Horizontal transfer of post-transcriptional operons by exosomal particles

The intercellular transfer of ribonucleoproteins containing specific RNA subsets from a donor cell to a recipient cell is via exosomal particle release from the donor cell. This hypothesis is based upon the transfer of a coherent subset of mRNAs, microRNAs and possibly other components of the ribonome, but it has not been tested. This mechanism would provide the RNA templates and post-transcriptional regulators necessary for translational co-ordination of the transferred mRNAs in the recipient cell.