The nucleolus is a dynamic subnuclear compartment that has a number of different functions, but its primary role is to coordinate the production and assembly of ribosomes. For well over 100 years, pathologists have used changes in nucleolar number and size to stage diseases such as cancer. New information about the nucleolus' broader role within the cell is leading to the development of drugs which directly target its structure as therapies for disease. Traditionally, it has been difficult to develop high-throughput image analysis pipelines to measure nucleolar changes due to the broad range of morphologies observed. In this study, we describe a simple high-content image analysis algorithm using Harmony software (PerkinElmer), with a PhenoLOGIC™ machine-learning component, that can measure and classify three different nucleolar morphologies based on nucleolin and fibrillarin staining ("normal," "peri-nucleolar rings" and "dispersed"). We have utilized this algorithm to determine the changes in these classes of nucleolar morphologies over time with drugs known to alter nucleolar structure. This approach could be further adapted to include other parameters required for the identification of new therapies that directly target the nucleolus.
The nucleophosmin (NPM1) gene encodes for the most abundant nucleolar protein. Thanks to its property to act as histone chaperone and to shuttle between the nucleus and cytoplasm, the NPM1 protein is involved in multiple cellular function that are here extensively reviewed and include the formation of the nucleolus through liquid-liquid phase separation, regulation of ribosome biogenesis and transport, control of DNA repair and centrosome duplication as well as response to nucleolar stress. NPM1 is mutated in about 30-35% of adult acute myeloid leukemia (AML).
The United Graduate School of Agricultural Sciences, Iwate University, Morioka, 020-8550, Japan; Graduate School of Agriculture and Life Science, Hiorosaki University, Hirosaki, 036-8561, Japan; Department of Biochemistry and Molecular Biology, Agriculture and Life Science, Hirosaki University, Hirosaki, 036-8561, Japan. Electronic address:
The precursor rRNA (pre-rRNA) processing pathway in Caenorhabditis elegans remains unidentified. We have determined the cleavage site within the internal transcribed spacer 2, which generates pre-rRNA f of 5.8S rRNA and pre-rRNA g of 26S rRNA.
The small nucleolar RNA host gene (SNHG) family may contribute to cancer development by creating long non-coding RNAs and affecting ribosome production and small nucleolar RNA formation.
A study analyzing 122 ovarian cancer samples found significant increases in the methylation levels of five SNHG family lncRNA genes, linking these changes to factors like tumor progression and metastasis.
Additionally, there was a notable co-methylation among four of these genes and predictions of their interactions with specific microRNAs, suggesting their collective role in ovarian cancer pathogenesis.
In the snoRNA host gene SNHG14, 29 consecutive introns each generate SNORD116, and 48 tandem introns encode SNORD115. Loss of SNORD116 expression, but not of SNORD115, is linked to the neurodevelopmental disease Prader-Willi syndrome. SNORD116 and SNORD115 resemble box C/D small nucleolar RNAs (snoRNAs) but lack known targets.
This study investigates why individuals with multimorbidity-two or more chronic conditions-are more prone to adverse outcomes after surgery. In our cohort, ninety-eight of 144 participants had multimorbidity. The myocardial transcriptome and metabolites involved in energy production were measured in 53 and 57 sequential participants, respectively.
