Nucleolin provides a link between RNA polymerase I transcription and pre-ribosome assembly

Abstract

Despite the identification of numerous factors involved in ribosomal RNA synthesis and maturation, the molecular mechanisms of ribosome biogenesis, and in particular the relationship between the different steps, are still largely unknown. We have investigated the consequences of an increased amount of a major nucleolar non-ribosomal protein, nucleolin, in Xenopus laevisstage VI oocytes on the production of ribosomal subunits. We show that a threefold increase in nucleolin leads to the complete absence of pre-rRNA maturation in addition to significant repression of RNA polymerase I transcription. Observation of "Christmas trees" by electron microscopy and analysis of the sedimentation properties of 40S pre-ribosomal particles suggest that an increased amount of nucleolin leads to incorrect packaging of the 40S particle. Interestingly, nucleolin affects the maturation of the 40S particle only when it is present at the time of transcription. These results indicate that nucleolin participates in the co-transcriptional packaging of the pre-rRNA, and that the quality of this packaging will determine whether the 40S precursor undergoes maturation or is degraded. The interaction of nucleolin with nascent pre-rRNA could help the co-transcriptional assembly on pre-rRNA of factors necessary for the subsequent maturation of the pre-ribosomal particle containing the 40S pre-rRNA.

Functional Implication of Nucleolin in the Mouse First Molar Development

“…The increase of nucleolin protein was also demonstrated in the regenerative liver after partial hepatectomy (32). Moreover, nucleolin was definitely implicated in ribosome biogenesis (9,10). Based on both our findings and those of previous reports, the expression of nucleolin is thus suggested to be closely related to the cell proliferation (33), and as a result, it is thus considered to participate in the tooth germ morphogenesis.…”

“…Nucleolin is a major nucleolar phosphoprotein that belongs to a large family of RNA-binding proteins (7,8). Nucleolin is thought to play a role in the pre-rRNA transcription and ribosome assembly that is implicated in the early stage of preribosomal ribonucleoprotein assembly and processing (9,10). The amount of nucleolin mRNA fluctuates in parallel with the status of DNA synthesis (11).…”

RNA-binding protein nucleolin in disease

“…Its acidic N-terminal region contains multiple phosphorylation sites, participates in the transcription of rRNA, and interacts with components of the pre-rRNA processing complex. 12 The central region of nucleolin contains four RNA-recognition motifs (RRMs) and mediates the interaction with mRNAs and pre-rRNA. 13,14 The C-terminal region of nucleolin contains an arginine/glycine-rich domain (RGG), through which nucleolin can interact with target mRNAs as well as with other proteins, including ribosomal proteins.…”

Characterization of AtNUC-L1 Reveals a Central Role of Nucleolin in Nucleolus Organization and Silencing of AtNUC-L2 Gene in Arabidopsis

“…Several nonribosomal nucleolar proteins as well as many small nucleolar ribonucleolar protein complexes (snoRNPs) have been implicated in the different steps of rRNA production and ribosome assembly (Fromont-Racine et al, 2003). Nucleolin is one of the most abundant nonribosomal proteins in the nucleolus, where it plays a key role in the different steps involved in ribosome biogenesis, including RNA polymerase (Pol) I transcription and processing of pre-rRNA (Ginisty et al, 1998;Roger et al, 2003), assembly and nucleocytoplasmic transport of ribosome particles . Nucleolin and nucleolin-like proteins have been described in a large variety of organisms, including Chinese hamster, mouse, rat, human, chicken, frog, yeast, and plants (for review, see Ginisty et al, 1999).…”

“…However, mutations that abolish nucleolin gene expression have not yet been reported in a higher organism. Thus, most of our knowledge on the function of this protein in higher eukaryotic cells comes from in vitro studies using acellular systems, microinjection experiments, or overexpression of a nucleolin transgene in Xenopus oocytes (Yanagida et al, 2001;Roger et al, 2002Roger et al, , 2003. Only two reports have described the effect of reduction of nucleolin in higher organisms.…”