High impact information on NSR1

• The NH2-terminal domain of Fpr3 contains long stretches of acidic residues alternating with blocks of basic residues, a structure that resembles sequences found in nucleolar proteins, including S. cerevisiae NSR1 and mammalian nucleolin [1].
• NSR1 has three regions: an acidic/serine-rich NH2 terminus, two RNA recognition motifs, and a glycine/arginine-rich COOH terminus [2].
• Interestingly, the NSR1 protein has two RNA recognition motifs, as well as an acidic NH2 terminus containing a series of serine clusters, and a basic COOH terminus containing arg-gly repeats [3].
• We have also shown that NSR1 (p67) is required for normal cell growth [3].
• We report here the isolation and characterization of the nucMs1 alfalfa cDNA, whose predicted amino acid sequence structurally resembles the yeast Nsr1 protein and animal nucleolins [4].

Biological context of NSR1

• NSR1, a 67-kD nucleolar protein, was originally identified in our laboratory as a nuclear localization signal binding protein, and has subsequently been found to be involved in ribosome biogenesis [2].
• The yeast nucleolar protein-encoding gene NSR1 was isolated by low-stringency screening of a yeast genomic library with the human heterogeneous nuclear ribonucleoprotein type A1 (hnRNP A1) cDNA probe, and was mapped to chromosome VII [5].
• The carboxyl-terminal half of NSR1, consisting of two tandemly repeated putative RNA-binding domains and a glycine/arginine-rich domain, has 37% amino acid sequence identity with the same part of mammalian nucleolin, while no sequence similarities are found between their amino-terminal regions [6].
• We report here the regulation of NSR1 gene expression and the effect of nsr1 deletion on growth and pre-rRNA processing after cold shock [7].
• Developmental and cell cycle regulation of alfalfa nucMs1, a plant homolog of the yeast Nsr1 and mammalian nucleolin [4].

Anatomical context of NSR1

• The nuclear localization sequence-binding protein is not extracted from the nuclear envelope with nonionic detergents and only partially extracted with high-salt buffer or 8 M urea, suggestive of a tight association with the nuclear envelope [8].

Associations of NSR1 with chemical compounds

• Among the few proteins of the eukaryotic nucleolus that have been characterized, four proteins, nucleolin, fibrillarin, SSB1 and NSR1, possess a common structural motif, the GAR domain, which is rich in glycine and arginine residues [9].
• Yeast strains carrying a deletion of the NSR1 gene have a defect in rRNA processing, an aberrant ribosome profile and are sensitive to the drug paromomycin [10].
• A comparison between the Nsr1 and hnRNP A1 proteins, based on homopolymer RNA binding to their structural domains in vitro, revealed a striking biochemical similarity [5].
• The 67 amino acid carboxyl-terminal domain (P67) of human propionyl-CoA carboxylase alpha subunit can be metabolically biotinylated at a fixed lysine residue [11].

Physical interactions of NSR1

• Our findings are consistent with the notion that nucleolar localization is a result of the binding interactions of various domains of NSR1 within the nucleolus rather than the presence of a specific nucleolar targeting signal [2].

Other interactions of NSR1

• Three of the radiolabeled proteins were confirmed to be Gar1p, Nop1p, and Nsr1p [12].
• Among these, ACT1 was isolated four times, and NSR1 three times [13].
• Both Nsr1p and Gbp2p bind specifically to yeast single strand (TG1-3)n DNA in vitro [14].
• The NSR1 gene product is involved in ribosomal RNA production and ribosome assembly in Saccharomyces cerevisiae [10].

Analytical, diagnostic and therapeutic context of NSR1

• These results suggest that when combined with P67-based biotinylation, anti-TfR IgG3-Av could serve as a universal delivery vector for targeted chemotherapy of cancer [11].

References