Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered bacterial second messenger implicated in the control of cell wall metabolism, osmotic stress responses, and sporulation. However, the mechanisms by which c-di-AMP triggers these physiological responses have remained largely unknown. Intriguingly, a candidate riboswitch class called ydaO associates with numerous genes involved in these same processes. Although a representative ydaO motif RNA recently was reported to weakly bind ATP, we report that numerous members of this noncoding RNA class selectively respond to c-di-AMP with sub-nanomolar affinity. Our findings resolve the mystery regarding the primary ligand for this extremely common riboswitch class and expose a major portion of the super-regulon of genes that are controlled by the widespread bacterial second messenger c-di-AMP.

Lamina-associated polypeptide (LAP) 2α is a LEM (lamina-associated polypeptide emerin MAN1) family protein associated with nucleoplasmic A-type lamins and chromatin. Using live cell imaging and fluorescence microscopy we demonstrate that LAP2α was mostly cytoplasmic in metaphase and associated with telomeres in anaphase. Telomeric LAP2α clusters grew in size, formed `core' structures on chromatin adjacent to the spindle in telophase, and translocated to the nucleoplasm in G1 phase. A subfraction of lamin C and emerin followed LAP2α to the core region early on, whereas LAP2β, lamin B receptor and lamin B initially bound to more peripheral regions of chromatin, before they spread to core structures with different kinetics. Furthermore, the DNA-crosslinking protein barrier-to-autointegration factor (BAF) bound to LAP2α in vitro and in mitotic extracts, and subfractions of BAF relocalized to core structures with LAP2α. We propose that LAP2α and a subfraction of BAF form defined complexes in chromatin core regions and may be involved in chromatin reorganization during early stages of nuclear assembly.

DNA phosphoester bonds are exceedingly resistant to hydrolysis in the absence of chemical or enzymatic catalysts. This property is particularly important for organisms with large genomes, as resistance to hydrolytic degradation permits the long-term storage of genetic information. Here we report the creation and analysis of two classes of engineered deoxyribozymes that selectively and rapidly hydrolyze DNA. Members of class I deoxyribozymes carry a catalytic core composed of only 15 conserved nucleotides and attain an observed rate constant (kobs) of ~1 min−1 when incubated near neutral pH in the presence of Zn2+. Natural DNA sequences conforming to the class I consensus sequence and structure were found that undergo hydrolysis under selection conditions (2 mM Zn2+, pH 7), which demonstrates that the inherent structure of certain DNA regions might promote catalytic reactions leading to genomic instability.