Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation

A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules

Efficacy and safety of a TIA/stroke electronic support tool (FASTEST) trial: Study protocol

<p>Abstract</p> <p>Background</p> <p>Strokes are a common cause of adult disability and mortality worldwide. Transient ischaemic attacks (TIA) are associated with a high risk of subsequent stroke, and rapid intervention has the potential to reduce stroke burden. This study will assess a novel electronic decision support (EDS) tool to allow general practitioners (GPs) to implement evidence-based care rapidly without full reliance on specialists.</p> <p>Methods/design</p> <p>This is a cluster randomized controlled trial comparing TIA/stroke management of GPs with access to the EDS tool versus usual care. The intervention period is 12 months with a 3-month follow-up period for individual patients. Primary outcomes consist of stroke within 90 days of presenting event and adherence to the New Zealand national TIA guideline.</p> <p>Discussion</p> <p>A positive study will provide strong evidence for widespread implementation of this tool in practice and has the potential to improve key outcomes for patients and reduce the burden of stroke.</p> <p>Trial registration</p> <p>Australia New Zealand Clinical Trials Registry ACTRN12611000792921</p