Figure 11.

Model of ribosomal biogenesis regulated by PARP-1. rDNA gene is transcribed into the 45S rRNA precursor (pre-rRNA), which is subsequently modified and processed into 5.8S, 18S, and 28S rRNAs by various rRNA-processing and rRNA-modifying factors. These rRNAs assemble with ribosomal proteins and preribosomal particles and then exit from the nucleus to become functional ribosomes in the cytoplasm. PARylated PARP-1 within rDNA contributes to formation of the dynamic PAR network in the nucleolus. This dynamic PAR network plays an essential role in rRNA processing, modification, and the loading of subsets of ribosomal proteins by regulating the localization of nucleolar-specific proteins in proximity to precursor rRNA in the nucleoli of Drosophila. PARP-1 mutants express a deletion in the PARP-1 protein or disruption of PARP-1 enzymatic activity, which leads to (1) altered subcellular localization of nucleolar-specific proteins, (2) nucleolar fragmentation, (3) delayed RNA processing, (4) a significant increase in rRNA intermediates, and (5) a decrease in ribosome levels.^91,221