A 58-year-old man comes to the office with a persistent dry cough. He also has involuntarily lost 10 kg (22 lb) over the past 3 months. The patient drinks 2 or 3 beers daily and has a 40-pack-year smoking history. Physical examination shows dullness to percussion over the right lower lung base. CT scan of the chest reveals a right-sided pleural effusion and a mass in the lower lobe of the right lung. Microscopic examination of the mass demonstrates malignant cells with large nuclei that contain prominent, round, basophilic bodies, as shown in the image below:
Show Explanatory Sources
Which of the following enzymes is most likely to function only within this basophilic region of the nucleus?
Synthesis & function of eukaryotic RNA | ||
Synthesizing polymerase | Type of RNA produced | Function |
RNA polymerase I | 18S, 5.8S & 28S ribosomal RNA | Forms essential ribosomal components |
RNA polymerase II | mRNA | Translated by ribosomes to form specific proteins |
Small nuclear RNA | Involved in mRNA splicing & transcription regulation | |
MicroRNA | Causes gene silencing via translation arrest or mRNA degradation | |
RNA polymerase III | Transfer RNA | Adaptor molecule linking codons with specific amino acids |
5S ribosomal RNA | Essential component of 60S ribosomal subunit | |
mRNA = messenger RNA. | ||
This patient's biopsy demonstrates malignant cells with prominent nucleoli, which appear as round, dense, basophilic (ie, dark blue to purple) intranuclear bodies on hematoxylin and eosin staining. The nucleolus is the primary site of ribosomal RNA (rRNA) transcription. Copies of the 45S pre-rRNA gene are arranged in clusters (nucleolar organizing regions) on multiple chromosomes; these regions come together in the nucleus to form the nucleolus. RNA polymerase I functions exclusively within the nucleolus to transcribe the 45S pre-rRNA gene into a single transcript that is subsequently processed into mature 18S, 5.8S, and 28S rRNAs.
In addition to rRNA transcription, the nucleolus is involved in the maturation and assembly of ribosomal subunits. Ribosomal proteins, which are synthesized in the cytoplasm, are transported into the nucleolus, where they combine with rRNA to form immature 40S and 60S subunits. These subunits are then shuttled via nuclear pores to the cytoplasm, where they ultimately participate in protein synthesis.
The regulation of ribosomal synthesis occurs in part by controlling the number of active rRNA genes. Generally, as cells become more differentiated, growth slows and the cells require fewer ribosomes for protein production. In contrast, malignant cells with high metabolic activity usually have a large number of active rRNA genes and prominent nucleoli.
(Choice A) Peptidyltransferase catalyzes peptide bond formation during protein synthesis, which occurs in mature ribosomes found in the cytoplasm.
(Choice C) RNA polymerase II synthesizes messenger RNA (mRNA), small nuclear RNA (snRNA), and microRNA (miRNA) in the nucleus. It is the most highly regulated of the 3 RNA polymerases, with its function determined by multiple transcription factors and epigenetic processes.
(Choice D) Ubiquitin ligase attaches ubiquitin molecules to proteins in the cytoplasm, tagging them for degradation in the cell's proteasome complex. The ubiquitin-proteasome pathway is important for the degradation of short-lived, senescent, or abnormal (eg, denatured, misfolded) proteins.
Educational objective:
The nucleolus is the site of ribosomal RNA (rRNA) transcription and ribosomal subunit assembly. RNA polymerase I functions exclusively within the nucleolus to transcribe the 45S pre-rRNA gene, which codes for most of the rRNA components (18S, 5.8S, and 28S rRNAs).