IT’S THE LITTLE THINGS: AN EXPLORATION OF SMALL RNAS AND SELFISH GENETIC ELEMENTS OF THE HUMAN BACTERIAL PATHOGENS COXIELLA BURNETII AND BARTONELLA BACILLIFORMIS

Coxiella burnetii is a Gram-negative gammaproteobacterium and zoonotic agent of Q fever in humans. Previous work in our lab has demonstrated that C. burnetii codes for several small RNAs (sRNAs) that are differentially expressed between in vivo and in vitro growth conditions. sRNAs serve as post-transcriptional regulatory effectors involved in the control of nearly all biological processes. We demonstrated that several of the identified sRNAs, namely Coxiella burnetii small RNA 3 (CbsR3), Cbsr13, and CbsR16, represent members of two novel families of miniature inverted-repeat transposable elements (MITEs), termed QMITE1 and QMITE2. Furthermore, we have characterized a highly expressed, infection-specific sRNA, CbsR12, and have determined that it is necessary for expansion of the C. burnetii intracellular niche in a human monocyte-derived alveolar macrophage cell line. We have determined that CbsR12 may participate in broad gene regulation by acting as an RNA sponge for the global regulatory RNA-binding protein CsrA. Additionally, CbsR12 is a trans-acting sRNA that targets transcripts of the carA, metK, and cvpD genes in vitro and in vivo. Bartonella bacilliformis is a Gram-negative alphaproteobacterium and the etiological agent of Carrión\u27s disease in humans. B. bacilliformis is spread between humans through the bite of female phlebotomine sand flies. As a result, the pathogen encounters significant environmental shifts during its life cycle, including changes in pH and temperature. Bacterial sRNAs can serve as a means of rapid regulation under shifting environmental conditions. We therefore performed total RNA-sequencing analyses on B. bacilliformis grown in vitro then shifted to one of ten distinct conditions that simulate various environments encountered by the pathogen during its life cycle. From this, we identified 160 sRNAs significantly expressed under at least one of the conditions tested. Northern blot analysis was used to confirm the expression of eight novel sRNAs. We also characterized a Bartonella bacilliformis group I intron (BbgpI) that disrupts an un-annotated tRNACCUArg gene and determined that the intron splices in vivo and self-splices in vitro. Furthermore, we verified the predicted molecular targeting of a sand fly-specific sRNA, Bartonella bacilliformis small RNA 9 (BbsR9), to transcripts of the ftsH, nuoF, and gcvT genes, in vitro

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

© 2020, The Author(s). The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975)