Because the transcriptional machinery is inactive throughout late stages of oogenesis and early stages of embryogenesis, the initial development of the embryo is driven by post-transcriptional regulation of maternally deposited mRNA. In Drosophila, this post-transcriptional regulation occurs at specialized sites called P- bodies. While P bodies contain proteins required for mRNA degradation, translational control, and microRNA processing, the complete composition of the P body is unknown. Recent work on the biochemistry of the P body has identified a novel protein of unknown function called Winnebago. Winnebago contains an atypical conserved ATPase motif homologous with the cyclo-ligase human methenyltetrahydrofolate synthetase (MTHFS) and a conserved RNA recognition motif suggesting that Winnebago may be a novel RNA modifying enzyme. Consistent with this, the substrate binding site of the Winnebago and its archaebacterial homologs are not conserved with the human MTHFS, indicating that Winnebago has a unique class of substrate. In this study, Swinn, the Winnebago homolog from Sulfolobus, was purified and it was demonstrated that it is an ATPase. We also found that Swinn does not use the normal substrates of MTHFS, arguing that it acts on a novel class of cyclo-ligase substrates. This work lays the groundwork for future studies to identify the substrate of the Winnebago family of ATPases and their role in RNA regulation

Identification of the cis-regulatory elements controlling cell-type specific gene expression patterns is essential for understanding the origin of cellular diversity. Conventional assays to map regulatory elements via open chromatin analysis of primary tissues is hindered by sample heterogeneity. Single cell analysis of accessible chromatin (scATAC-seq) can overcome this limitation. However, the high-level noise of each single cell profile and the large volume of data pose unique computational challenges. Here, we introduce SnapATAC, a software package for analyzing scATAC-seq datasets. SnapATAC dissects cellular heterogeneity in an unbiased manner and map the trajectories of cellular states. Using the Nyström method, SnapATAC can process data from up to a million cells. Furthermore, SnapATAC incorporates existing tools into a comprehensive package for analyzing single cell ATAC-seq dataset. As demonstration of its utility, SnapATAC is applied to 55,592 single-nucleus ATAC-seq profiles from the mouse secondary motor cortex. The analysis reveals ~370,000 candidate regulatory elements in 31 distinct cell populations in this brain region and inferred candidate cell-type specific transcriptional regulators.