Flamholz, Z. | Search bioRxiv

bioRxiv2022

Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis

Stem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that pseudouridylation of ribosomal RNA (rRNA) mediated by the H/ACA box is required for ribosome biogenesis and oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of mRNAs that are enriched for CAG repeats and encode polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing TOR activity to elevate ribosome levels in H/ACA box-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.

developmental biology↗

bioRxiv2019

FAIRshake: toolkit to evaluate the findability, accessibility, interoperability, and reusability of research digital resources

As more datasets, tools, workflows, APIs, and other digital resources are produced by the research community, it is becoming increasingly difficult to harmonize and organize these efforts for maximal synergistic integrated utilization. The Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles have prompted many stakeholders to consider strategies for tackling this challenge by making these digital resources follow common standards and best practices so that they can become more integrated and organized. Faced with the question of how to make digital resources more FAIR, it has become imperative to measure what it means to be FAIR. The diversity of resources, communities, and stakeholders have different goals and use cases and this makes assessment of FAIRness particularly challenging. To begin resolving this challenge, the FAIRshake toolkit was developed to enable the establishment of community-driven FAIR metrics and rubrics paired with manual, semi- and fully-automated FAIR assessment capabilities. The FAIRshake toolkit contains a database that lists registered digital resources, with their associated metrics, rubrics, and assessments. The FAIRshake toolkit also has a browser extension and a bookmarklet that enables viewing and submitting assessments from any website. The FAIR assessment results are visualized as an insignia that can be viewed on the FAIRshake website, or embedded within hosting websites. Using FAIRshake, a variety of bioinformatics tools, datasets listed on dbGaP, APIs registered in SmartAPI, workflows in Dockstore, and other biomedical digital resources were manually and automatically assessed for FAIRness. In each case, the assessments revealed room for improvement, which prompted enhancements that significantly upgraded FAIRness scores of several digital resources.

bioinformatics↗