to Explore Nucleolar Stress.

Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy depending on the cell type.

Nucleolar stress in neuroblasts, a model for human ribosomopathies.

Different stem cells or progenitor cells display variable threshold requirements for functional ribosomes. This is particularly true for several human ribosomopathies in which select embryonic neural crest cells or adult bone marrow stem cells, but not others, show lethality due to failures in ribosome biogenesis or function (now known as nucleolar stress). To determine if various neuroblasts display differential sensitivities to nucleolar stress, we used CRISPR-Cas9 to disrupt the gene that encodes two splice variant ribosome biogenesis factors (RBFs).

The Nopp140 gene in Drosophila melanogaster displays length polymorphisms in its large repetitive second exon.

Nopp140, often called the nucleolar and Cajal body phosphoprotein (NOLC1), is an evolutionarily conserved chaperone for the transcription and processing of rRNA during ribosome subunit assembly. Metazoan Nopp140 contains an amino terminal LisH dimerization domain and a highly conserved carboxyl domain. A large central domain consists of alternating basic and acidic motifs of low sequence complexity.