Highlights d LARP7 interacts simultaneously with the U6 snRNA and U6specific C/D box snoRNAs d Depletion of LARP7 results in reduced 2 0 -O-methylation of the U6 snRNA d Changes in alternative splicing are observed in the absence of LARP7 d A LARP7 mutation causes splicing alterations in Alazami syndrome patients

Sarcoidosis is a granulomatous disease of unknown etiology. The disease has an important inflammatory and immune component; however, its immunopathogenesis is not completely understood. Recently, the role of microRNAs (miRNAs), the small non-coding RNAs, has attracted attention as both being involved in pathogenesis and serving as disease markers. Accordingly, changes in the expression of some miRNAs have been also associated with different autoimmune pathologies. However, not much is known about the role of miRNAs in sarcoidosis. Therefore, the aim of this study was to compare the level of expression of selected miRNAs in healthy individuals and patients with sarcoidosis. We detected significantly increased level of miR-34a in peripheral blood mononuclear cells isolated from sarcoidosis patients. Moreover, significantly up-regulated levels of interferon (IFN)-γ, IFN-γ inducible protein (IP-10) and vascular endothelial growth factor were detected in sera of patients when compared to healthy subjects. Our results add to a known inflammatory component in sarcoidosis. Changes in the levels of miR-34a may suggest its involvement in the pathology of this disease.

Recent advances in metagenomics provided a valuable alternative to culture-based approaches for better sampling viral diversity. However, some of newly identified viruses lack sequence similarity to any of previously sequenced ones, and cannot be easily assigned to their hosts. Here we present a bioinformatic approach to this problem. We developed classifiers capable of distinguishing eukaryotic viruses from the phages achieving almost 95% prediction accuracy. The classifiers are wrapped in Host Taxon Predictor (HTP) software written in Python which is freely available at https://github.com/wojciech-galan/viruses_classifier . HTP’s performance was later demonstrated on a collection of newly identified viral genomes and genome fragments. In summary, HTP is a culture- and alignment-free approach for distinction between phages and eukaryotic viruses. We have also shown that it is possible to further extend our method to go up the evolutionary tree and predict whether a virus can infect narrower taxa.

Chemerin is a chemoattractant protein with adipokine properties encoded by the retinoic acid receptor responder 2 (RARRES2) gene. it has gained more attention in the past few years due to its multilevel impact on metabolism and immune responses. However, mechanisms controlling the constitutive and regulated expression of RARRES2 in a variety of cell types remain obscure. To our knowledge, this report is the first to show that DNA methylation plays an important role in the cell-specific expression of RARRES2 in adipocytes, hepatocytes, and B lymphocytes. Using luciferase reporter assays, we determined the proximal fragment of the RARRES2 gene promoter, located from − 252 to + 258 bp, to be a key regulator of transcription. Moreover, we showed that chemerin expression is regulated in murine adipocytes by acute-phase cytokines, interleukin 1β and oncostatin M. in contrast with adipocytes, these cytokines exerted a weak, if any, response in mouse hepatocytes, suggesting that the effects of IL-1β and OSM on chemerin expression is specific to fat tissue. Together, our findings highlight previously uncharacterized mediators and mechanisms that control chemerin expression. Chemerin is a small (18 kDa) multifunctional protein capable of regulating different biological processes, including immune cell migration, adipogenesis, osteoblastogenesis, angiogenesis, myogenesis, and glucose homeostasis 1. Moreover, it shows broad-spectrum antimicrobial activity in both human and mouse epidermis, suggesting it plays a role in maintaining skin-barrier homeostasis 2,3. Chemerin-induced signaling is mediated predominantly through chemokine-like receptor 1 (CMKLR1), which is expressed by many cells including plasmacytoid dendritic cells (pDCs), macrophages, natural killer (NK) cells, adipocytes, hepatocytes, and keratinocytes 2,4-9. Chemerin is secreted as pro-chemerin and circulates in plasma as an inactive precursor protein (Chem163S) that can subsequently be activated through posttranslational carboxyl-terminal processing by a variety of proteinases 10,11. The gene encoding chemerin is known as retinoic acid receptor responder 2 (RARRES2) 12 , or as tazaroteneinduced gene 2 (TIG2) given it was first discovered in tazarotene-treated psoriatic skin lesions 13,14. Liver and adipose tissue are reported to be the major sites of chemerin production; nonetheless, RARRES2 mRNA is detectable in many other tissues, including the adrenal glands, ovaries, pancreas, lungs, kidney, and skin 2,15. Chemerin