Malat1 affects transcription and splicing through distinct pathways in mouse embryonic stem cells.

Malat1 is a long-noncoding RNA with critical roles in gene regulation and cancer metastasis, however its functional role in stem cells is largely unexplored. We here perform a nuclear knockdown of Malat1 in mouse embryonic stem cells, causing the de-regulation of 320 genes and aberrant splicing of 90 transcripts, some of which potentially affecting the translated protein sequence. We find evidence that Malat1 directly interacts with gene bodies and aberrantly spliced transcripts, and that it locates upstream of down-regulated genes at their putative enhancer regions, in agreement with functional genomics data. Consistent with this, we find these genes affected at both exon and intron levels, suggesting that they are transcriptionally regulated by Malat1. Besides, the down-regulated genes are regulated by specific transcription factors and bear both activating and repressive chromatin marks, suggesting that some of them might be regulated by bivalent promoters. We propose a model in which Malat1 facilitates the transcription of genes involved in chromatid dynamics and mitosis in one pathway, and affects the splicing of transcripts that are themselves involved in RNA processing in a distinct pathway. Lastly, we compare our findings with Malat1 perturbation studies performed in other cell systems and in vivo.

MirGeneDB 2.1: toward a complete sampling of all major animal phyla.

We describe an update of MirGeneDB, the manually curated microRNA gene database. Adhering to uniform and consistent criteria for microRNA annotation and nomenclature, we substantially expanded MirGeneDB with 30 additional species representing previously missing metazoan phyla such as sponges, jellyfish, rotifers and flatworms. MirGeneDB 2.1 now consists of 75 species spanning over ∼800 million years of animal evolution, and contains a total number of 16 670 microRNAs from 1549 families. Over 6000 microRNAs were added in this update using ∼550 datasets with ∼7.5 billion sequencing reads. By adding new phylogenetically important species, especially those relevant for the study of whole genome duplication events, and through updating evolutionary nodes of origin for many families and genes, we were able to substantially refine our nomenclature system. All changes are traceable in the specifically developed MirGeneDB version tracker. The performance of read-pages is improved and microRNA expression matrices for all tissues and species are now also downloadable. Altogether, this update represents a significant step toward a complete sampling of all major metazoan phyla, and a widely needed foundation for comparative microRNA genomics and transcriptomics studies. MirGeneDB 2.1 is part of RNAcentral and Elixir Norway, publicly and freely available at http://www.mirgenedb.org/.

The Body Size of Stimulus Conspecifics Affects Social Preference in a Binary Choice Task in Wild-Type, But Not in dyrk1aa Mutant, Zebrafish.

The zebrafish has become an appropriate animal model in the analysis of numerous human brain disorders. A variety of neuropsychiatric conditions and neurodevelopmental disorders are comorbid with abnormal social behavior. Given the translational relevance of zebrafish, multidisciplinary studies employing behavioral, neurobiological, and molecular methods with this species may provide insights into human central nervous system (CNS) disorders. Many of these studies impinge upon our ability to properly induce and quantify the behavior of zebrafish, a relatively understudied aspect of this species. In this study, we investigate how the body size of conspecifics relative to that of the test subject influences social (shoaling) responses in zebrafish. We found a robust preference by wild-type (WT) test zebrafish toward big conspecifics, but not toward smaller conspecifics. Additionally, we tested an autism-relevant zebrafish knockout (KO) model. The dyrk1aa KO zebrafish showed impaired social preference compared with WT in the social behavior test. Our results confirm the effect of relative body size on social preference and that the social preference task developed for zebrafish may uncover the function of genes and biological mechanisms potentially associated with human CNS disorders.