Abstract
RNA–protein interactions are crucial for most biological processes in all organisms. However, it appears that the complexity of RNA-based regulation increases with the complexity of the organism, creating additional regulatory circuits, the scope of which is only now being revealed. It is becoming apparent that previously unappreciated features, such as disordered structural regions in proteins or non-coding regions in DNA leading to higher plasticity and pliability in RNA–protein complexes, are in fact essential for complex, precise and fine-tuned regulation. This review addresses the issue of the role of RNA–protein interactions in generating eukaryotic complexity, focusing on the newly characterized disordered RNA-binding motifs, moonlighting of metabolic enzymes, RNA-binding proteins interactions with different RNA species and their participation in regulatory networks of higher order.
Highlights
With the possible exception of the unestablished first stages in the evolution of life, RNA has always been accompanied by some proteins
The discovery of CRISPR– Cas9 RNA-guided interference shows that bacteria have at their disposal more sophisticated mechanisms involving RNA regulation employed in anti-phage defence [1]
In CUG-binding protein 2, which regulates the COX-2 transcript by binding to its 30 untranslated region (UTR), the RNA recognition motif (RRM) was shown to exist in distinct substates, enabling a conformational switch between low-affinity binding, associated with dynamic RNA scanning, and high-affinity binding with RNA target locking [31]
Summary
With the possible exception of the unestablished first stages in the evolution of life, RNA has always been accompanied by some proteins. Structural disorder allows for more flexible and dynamic RNA binding, which contributes to the precision of the cellular response to stress and signalling These new findings suggest that there is a whole new avenue of research to explore and that the role of RBPs in generating complexity may have been underestimated. Since only about 1–2% of the human genome encodes proteins and as much as 83 –85% is transcribed [3], we have a large proportion of transcripts with unassigned functions, transcriptome ‘dark matter’ The functions of these ‘junk’ transcripts are quite diverse, but mostly associated with fine-tuning of expression, providing a plethora of regulatory mechanisms, including direct regulation of protein activity. We will focus on other types of RNA binding, which may be a critical factor in eukaryotic complexity
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