Deep sequencing uncovers numerous small RNAs on all four replicons of the plant pathogen Agrobacterium tumefaciens

Agrobacterium species are capable of interkingdom gene transfer between bacteria and plants. The genome of Agrobacterium tumefaciens consists of a circular and a linear chromosome, the At-plasmid and the Ti-plasmid, which harbors bacterial virulence genes required for tumor formation in plants. Little is known about promoter sequences and the small RNA (sRNA) repertoire of this and other α-proteobacteria. We used a differential RNA sequencing (dRNA-seq) approach to map transcriptional start sites of 388 annotated genes and operons. In addition, a total number of 228 sRNAs was revealed from all four Agrobacterium replicons. Twenty-two of these were confirmed by independent RNA gel blot analysis and several sRNAs were differentially expressed in response to growth media, growth phase, temperature or pH. One sRNA from the Ti-plasmid was massively induced under virulence conditions. The presence of 76 cis-antisense sRNAs, two of them on the reverse strand of virulence genes, suggests considerable antisense transcription in Agrobacterium. The information gained from this study provides a valuable reservoir for an in-depth understanding of sRNA-mediated regulation of the complex physiology and infection process of Agrobacterium

Kleine regulatorische RNAs in Agrobacterium tumefaciens\textit {Agrobacterium tumefaciens}

$\textit {Agrobacterium tumefaciens}$ ist ein Pflanzen-pathogenes Bakterium. Überwiegende Teile dieser Arbeit befaßten sich damit kleine regulatorische RNAs (sRNAs) in diesem Organismus zu identifizieren und zu charakterisieren. Eine bioinformatische Vorhersage für sRNAs sowie Hochdurchsatz-cDNA-Sequenzierungen (RNA-seq) lieferten zahlreiche Kandidaten. Die sRNA AbcR1 verhindert die Translation von $\it atu2422$ und induziert die Degradation der mRNA. Das $\it atu2422$-Gen kodiert ein $\gamma$-Aminobuttersäure (GABA)-bindendes Protein. GABA ist am Abwehrmechanismus der Pflanze beteiligt. Eine Virulenz-induzierte sRNA sowie einige sRNAs, die auf dem Gegenstrang von Virulenz-Genen gefunden wurden, deuten auf einen Einfluss auf die Virulenz-Kaskade von $\it Agrobacterium$ hin. Ein drittes Teil-Projekt war dem RNA-Chaperon Hfq gewidmet. Eine $\it hfq$ Deletions-Mutante wies eine erhöhte Expression von ABC-Transportern, sowie signifikante Defizite im Wachstum, der Zell-Morphologie, der Motilität und der Tumor-Bildung auf

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele