Nucleolus

About: Nucleolus is a research topic. Over the lifetime, 5873 publications have been published within this topic receiving 232435 citations. The topic is also known as: GO:0005730 & cell nucleolus.

Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells.

Abstract: Many RNA regulatory proteins controlling pre-messenger RNA splicing contain serine:arginine (SR) repeats. Here, we found that these SR domains bound hydrogel droplets composed of fibrous polymers of the low-complexity domain of heterogeneous ribonucleoprotein A2 (hnRNPA2). Hydrogel binding was reversed upon phosphorylation of the SR domain by CDC2-like kinases 1 and 2 (CLK1/2). Mutated variants of the SR domains changing serine to glycine (SR-to-GR variants) also bound to hnRNPA2 hydrogels but were not affected by CLK1/2. When expressed in mammalian cells, these variants bound nucleoli. The translation products of the sense and antisense transcripts of the expansion repeats associated with the C9orf72 gene altered in neurodegenerative disease encode GRn and PRn repeat polypeptides. Both peptides bound to hnRNPA2 hydrogels independent of CLK1/2 activity. When applied to cultured cells, both peptides entered cells, migrated to the nucleus, bound nucleoli, and poisoned RNA biogenesis, which caused cell death.

Cellular and biochemical events in mammalian cells during and after recovery from physiological stress.

Abstract: We have examined and compared a number of cellular and biochemical events associated with the recovery process of rat fibroblasts placed under stress by different agents. Metabolic pulse-labeling studies of cells recovering from either heat-shock treatment, exposure to sodium arsenite, or exposure to an amino acid analogue of proline, L-azetidine 2-carboxylic acid, revealed interesting differences with respect to the individual stress proteins produced, their kinetics of induction, as well as the decay in their synthesis during the recovery period. In the initial periods of recovery, the major stress-induced 72-kD protein accumulates within the altered nucleoli in close association with the pre-ribosomal-containing granular region. During the later times of recovery from stress, the nucleoli begin to regain a normal morphology, show a corresponding loss of the 72-kD protein, and the majority of the protein now begins to accumulate within the cytoplasm in three distinct locales: the perinuclear region, along the perimeter of the cells, and finally in association with large phase-dense structures. These latter structures appear to consist of large aggregates of phase-dense material with no obvious encapsulating membrane. More interestingly we show, using double-label indirect immunofluorescence analysis, that much of the perinuclear and cell perimeter-distributed 72-kD protein coincides with the distribution of the cytoplasmic ribosomes. We discuss the possible implications of the presence of the 72-kD stress proteins within the pre-ribosomal-containing granular region of the nucleolus as well as its subsequent colocalization with cytoplasmic ribosomes in terms of the translational changes which occur in cells both during and after recovery from physiological stress.

The post-transcriptional steps of eukaryotic ribosome biogenesis.

Abstract: One of the most important tasks of any cell is to synthesize ribosomes. In eukaryotes, this process occurs sequentially in the nucleolus, the nucleoplasm and the cytoplasm. It involves the transcription and processing of pre-ribosomal RNAs, their proper folding and assembly with ribosomal proteins and the transport of the resulting pre-ribosomal particles to the cytoplasm where final maturation events occur. In addition to the protein and RNA constituents of the mature cytoplasmic ribosomes, this intricate process requires the intervention of numerous protein and small RNA trans-acting factors. These transiently interact with pre-ribosomal particles at various stages of their maturation. Most of the constituents of pre-ribosomal particles have probably now been identified and research in the field is starting to unravel the timing of their intervention and their precise mode of action. Moreover, quality control mechanisms are being discovered that monitor ribosome synthesis and degrade the RNA components of defective pre-ribosomal particles.