Optimizing RNA structures by sequence extensions using RNAcop

A key aspect of RNA secondary structure prediction is the identification of novel functional elements. This is a challenging task because these elements typically are embedded in longer transcripts where the borders between the element and flanking regions have to be defined. The flanking sequences impact the folding of the functional elements both at the level of computational analyses and when the element is extracted as a transcript for experimental analysis. Here, we analyze how different flanking region lengths impact folding into a constrained structure by computing probabilities of folding for different sizes of flanking regions. Our method, RNAcop (RNA context optimization by probability), is tested on known and de novo predicted structures. In vitro experiments support the computational analysis and suggest that for a number of structures, choosing proper lengths of flanking regions is critical. RNAcop is available as web server and stand-alone software via http://rth.dk/resources/rnacop

Making proteins in the powerhouse

Understanding regulation of mitochondrial DNA (mtDNA) expression is of considerable interest as mitochondrial dysfunction is important in human pathology and ageing. Similar to the situation in bacteria, there is no compartmentalization between transcription and translation in mitochondria; hence, both processes are likely to have a direct molecular crosstalk. Accumulating evidence suggests that there are important mechanisms for regulation of mammalian mtDNA expression at the posttranscriptional level. Regulation of mRNA maturation, mRNA stability, translational coordination, ribosomal biogenesis and translation itself, all form the basis for controlling oxidative phosphorylation capacity. Consequently, a wide variety of inherited human mitochondrial diseases are caused by mutations of nuclear genes regulating various aspects of mitochondrial translation. Furthermore, mutations of mtDNA, associated with human disease and ageing, often affect tRNA genes critical for mitochondrial translation. Recent advances in molecular understanding of mitochondrial translation regulation will likely provide novel avenues for modulating mitochondrial function to treat human disease.VetenskapsrådetAccepte