Fibrillarin is a protein found within the cells of eukaryotes, organisms whose cells have a nucleus and other organelles enclosed within membranes. It was first identified in 1985 through analyses using blood samples from patients with an autoimmune condition called scleroderma. This protein is primarily located in the nucleolus, a distinct, dense structure inside the cell’s nucleus. The nucleolus is the primary site for ribosome production within the cell. Fibrillarin plays a role in various cellular processes.
Fibrillarin’s Primary Role in Ribosome Production
Fibrillarin plays a role in ribosome biogenesis, the process by which cells assemble ribosomes, the molecular machines responsible for protein synthesis. This protein is a component of small nucleolar ribonucleoproteins (snoRNPs), specifically C/D box snoRNPs, which modify ribosomal RNA (rRNA). Fibrillarin acts as an S-adenosyl-L-methionine-dependent methyltransferase, adding methyl groups to specific locations on rRNA molecules.
This methylation process is a precise modification guided by snoRNAs. These modifications are essential for the proper folding, stability, and overall function of rRNA, which ensures the correct assembly of ribosomal subunits. Without these modifications, ribosomes might not form correctly or function efficiently, impacting the cell’s ability to produce proteins. The modification of rRNA by fibrillarin is fundamental for all living cells, underpinning the basic machinery of protein production.
Beyond Ribosomes: Other Cellular Functions of Fibrillarin
While its main function is in ribosome production, fibrillarin also participates in other cellular activities. It is involved in the processing of various small nucleolar RNAs (snoRNAs). These snoRNAs guide post-transcriptional modifications that affect different types of RNA within the cell.
Fibrillarin is also found in stress granules, temporary cellular compartments that form when cells experience environmental stress, such as heat shock or oxidative stress. These granules help cells survive by temporarily halting protein synthesis and storing messenger RNAs (mRNAs) and associated proteins. Fibrillarin’s presence in these structures suggests a role in the cell’s adaptive response to adverse conditions. Fibrillarin has also been implicated in other RNA processing events and cellular responses, including roles in viral progression and maintaining nuclear morphology.
Fibrillarin’s Link to Health and Disease
Fibrillarin’s involvement in cellular processes extends to human health and disease. It is associated with autoimmune conditions, particularly systemic sclerosis, also known as scleroderma. In about 4-10% of individuals with systemic sclerosis, autoantibodies are produced against fibrillarin, called anti-fibrillarin antibodies or anti-U3 RNP antibodies. These autoantibodies mistakenly target the body’s own fibrillarin, and their presence can be a diagnostic indicator for systemic sclerosis.
The presence of anti-fibrillarin antibodies in systemic sclerosis patients is linked to specific clinical features, including earlier disease onset and a higher likelihood of diffuse skin involvement. These patients may also experience more internal organ complications, such as pulmonary hypertension, muscle inflammation (myositis), heart involvement, and kidney problems. Altered fibrillarin expression levels have also been observed in certain types of cancer, indicating its involvement in tumor development and progression.