Non-canonical actions of Nogo-A and its receptors

Nogo-A is a myelin associated protein and one of the most potent neurite growth inhibitors in the central nervous system. Interference with Nogo-A signaling has thus been investigated as therapeutic target to promote functional recovery in CNS injuries. Still, the finding that Nogo-A presents a fairly ubiquitous expression in many types of neurons in different brain regions, in the eye and even in the inner ear suggests for further functions besides the neurite growth repression. Indeed, a growing number of studies identified a variety of functions including regulation of neuronal stem cells, modulation of microglial activity, inhibition of angiogenesis and interference with memory formation. Aim of the present commentary is to draw attention on these less well-known and sometimes controversial roles of Nogo-A. Furthermore, we are addressing the role of Nogo-A in neuropathological conditions such as ischemic stroke, schizophrenia and neurodegenerative diseases.

An intergenic non-coding RNA targets and regulates the ribosome in H. volcanii.

As translation is the final step in gene expression it is particularly important to understand the processes involved in translation regulation. It was shown in the last years that a class of RNA, the nonprotein-coding RNAs (ncRNAs), is involved in regulation of gene expression via various mechanisms (e.g. gene silencing by microRNAs). Almost all of these ncRNA discovered so far target the mRNA in order to modulate protein biosynthesis, this is rather unexpected considering the crucial role of the ribosome during gene expression. However, recent data from our laboratory showed that there is a new class of ncRNAs, which target the ribosome itself [Gebetsberger et al., 2012/ Pircher et al, 2014]. These so called ribosome-associated ncRNAs (rancRNAs) have an impact on translation regulation, mainly by interfering / modulating the rate of protein biosynthesis. The main goal of this project is to identify and describe novel potential regulatory rancRNAs in H. volcanii with the focus on intergenic candidates. Northern blot analyses already revealed interactions with the ribosome and showed differential expression of rancRNAs during different growth phases or under specific stress conditions. To investigate the biological relevance of these rancRNAs, knock-outs were generated in H. volcanii which were used for phenotypic characterization studies. The rancRNA s194 showed association with the 50S ribosomal subunit in vitro and in vivo and was capable of inhibiting peptide bond formation. These preliminary data for the rancRNA s194 make it an interesting candidate for further functional studies to identify the molecular mechanisms by which rancRNAs can modulate protein biosynthesis. Characterization of further rancRNA candidates are also underway.

Decomposing hierarchical alignment: Co-arguments as conditions on alignment and the limits of referential hierarchies as explanations in verb agreement

Apart from common cases of differential argument marking, referential hierarchies affect argument marking in two ways: (a) through hierarchical marking, where markers compete for a slot and the competition is resolved by a hierarchy, and (b) through co-argument sensitivity, where the marking of one argument depends on the properties of its co-argument. Here we show that while co-argument sensitivity cannot be analyzed in terms of hierarchical marking, hierarchical marking can be analyzed in terms of co-argument sensitivity. Once hierarchical effects on marking are analyzed in terms of co-argument sensitivity, it becomes possible to examine alignment patterns relative to referential categories in exactly the same way as one can examine alignment patterns relative to referential categories in cases of differential argument marking and indeed any other condition on alignment (such as tense or clause type). As a result, instances of hierarchical marking of any kind turn out not to present a special case in the typology of alignment, and there is no need for positing an additional non-basic alignment type such as “hierarchical alignment”. While hierarchies are not needed for descriptive and comparative purposes, we also cast doubt on their relevance in diachrony: examining two families for which hierarchical agreement has been postulated, Algonquian and Kiranti, we find only weak and very limited statistical evidence for agreement paradigms to have been shaped by a principled ranking of person categories.