A dual ribosomal system in the zebrafish soma and germline.

Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal ribosomes synthesized during oogenesis and stored in the egg, and somatic ribosomes, produced by the developing embryo after zygotic genome activation (ZGA). In zebrafish, these two ribosome types are expressed from different genomic loci and also differ in their ribosomal RNA (rRNA) sequence. To characterize this dual ribosome system further, we examined the expression patterns of maternal and somatic rRNAs during embryogenesis and in adult tissues.

Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network.

Unlabelled: Cyclin-dependent kinase 9 (CDK9) coordinates signaling events that regulate RNA polymerase II (Pol II) pause-release states. It is an important co-factor for transcription factors, such as MYC, that drive aberrant cell proliferation when their expression is deregulated. CDK9 modulation offers an approach for attenuating dysregulation in such transcriptional programs.

A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.

Disruptions in core cellular processes elicit stress responses that drive cell-state changes leading to organismal phenotypes. Perturbations in the splicing machinery cause widespread mis-splicing, resulting in p53-dependent cell-state changes that give rise to cell-type-specific phenotypes and disease. However, a unified framework for how cells respond to splicing perturbations, and how this response manifests itself in nuanced disease phenotypes, has yet to be established.

Nucleolus activity-dependent recruitment and biomolecular condensation by pH sensing.

DEAD-box ATPases are major regulators of biomolecular condensates and orchestrate diverse biochemical processes that are critical for the functioning of cells. How DEAD-box proteins are selectively recruited to their respective biomolecular condensates is unknown. We explored this in the context of the nucleolus and DEAD-box protein DDX21.

SBDS rescues survival of zebrafish in a dose-dependent manner independently of Tp53.

Defects in ribosomal biogenesis profoundly affect organismal development and cellular function, and these ribosomopathies produce a variety of phenotypes. One ribosomopathy, Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, pancreatic exocrine insufficiency, and skeletal anomalies. SDS results from biallelic mutations in , which encodes a ribosome assembly factor.