Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli

Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis

RNA processing of beta-globin transcripts containing 5' flanking and structural gene sequences.

RNA species have been identified in murine erythroid cells which contain both 5' flanking and structural gene sequences from the beta maj globin gene. Two nonpolyadenylated RNA transcripts, average 3700 and 1800-1900 nucleotides long, were identified by denaturing agarose gel electrophoresis and were found to hybridize to both 5' and 3' beta maj globin flanking sequences. This finding suggests that transcription initiated in the 5' flanking region does proceed past the polyadenylation site. The apparent higher concentration of the 5' flanking sequences in precursor RNA molecules, as compared to mature polyadenylated globin mRNA, suggests increased precursor stability of beta globin transcripts initiated in the 5' flanking region