rRNA 2'-O-methyltransferase fibrillarin is an enzyme that in humans is encoded by the FBLgene.[5][6][7]
Function
This gene product is a component of a nucleolar small nuclear ribonucleoprotein (snRNP) particle thought to participate in the first step in processing pre-ribosomal (r)RNA. It is associated with the U3, U8, and U13 small nucleolar RNAs and is located in the dense fibrillar component (DFC) of the nucleolus. The encoded protein contains an N-terminal repetitive domain that is rich in glycine and arginine residues, like fibrillarins in other species. Its central region resembles an RNA-binding domain and contains an RNP consensus sequence. Antisera from approximately 8% of humans with the autoimmune disease scleroderma recognize fibrillarin.[7]
Fibrillarin is a component of several ribonucleoproteins including a nucleolar small nuclear ribonucleoprotein (SnRNP) and one of the two classes of small nucleolar ribonucleoproteins (snoRNPs). SnRNAs function in RNA splicing while snoRNPs function in ribosomal RNA processing.
Fibrillarin is associated with U3, U8 and U13 small nuclear RNAs in mammals and is similar to the yeast NOP1 protein. Fibrillarin has a well conserved sequence of around 320 amino acids, and contains 3 domains, an N-terminal Gly/Arg-rich region; a central domain resembling other RNA-binding proteins and containing an RNP-2-like consensus sequence; and a C-terminal alpha-helical domain. An evolutionarily related pre-rRNA processing protein, which lacks the Gly/Arg-rich domain, has been found in various archaea.
A study by Schultz et al. indicated that the K-turn binding 15.5-kDa protein (called Snu13 in yeast) interacts with spliceosome proteins hPRP31, hPRP3, hPRP4, CYPH and the small nucleolar ribonucleoproteins NOP56, NOP58, and fibrillarin. The 15.5-kDa protein has sequence similarity to other RNA-binding proteins such as ribosomal proteins S12, L7a, and L30 and the snoRNP protein NHP2. The U4/U6 snRNP contains 15.5-kDa protein.[8] The 15.5-kDa protein also exists in a ribonucleoprotein complex that binds the U3 box B/C motif. The 15.5-kDa protein also exists as one of the four core proteins of the C/D small nucleolar ribonucleoprotein that mediates methylation of pre-ribosomal RNAs.
Structural evidence supporting the idea that fibrillarin is the snoRNA methyltransferase has been reviewed.[9]
^Nicol SM, Causevic M, Prescott AR, Fuller-Pace FV (Jun 2000). "The nuclear DEAD box RNA helicase p68 interacts with the nucleolar protein fibrillarin and colocalizes specifically in nascent nucleoli during telophase". Experimental Cell Research. 257 (2): 272–80. doi:10.1006/excr.2000.4886. PMID10837141.
^Pellizzoni L, Baccon J, Charroux B, Dreyfuss G (Jul 2001). "The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1". Current Biology. 11 (14): 1079–88. doi:10.1016/S0960-9822(01)00316-5. PMID11509230.
Human neuroblastoma, (SH-SY5Y) cells stained with antibody to fibrillarin in green, antibody to neurofilament NF-H in red and DNA in dark blue, The fibrillarin antibody binds to spots in the nucleus corresponding to nucleoli. The nucleoli also contain DNA and so appear as pale blue dots. The neurofilament NF-H antibody binds to cytoplasmic intermediate or 10nm filaments. Image, antibodies and staining by EnCor Biotechnology Inc.
Okano Y, Steen VD, Medsger TA (Jan 1992). "Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis". Arthritis and Rheumatism. 35 (1): 95–100. doi:10.1002/art.1780350114. PMID1731817.
Lischwe MA, Ochs RL, Reddy R, Cook RG, Yeoman LC, Tan EM, Reichlin M, Busch H (Nov 1985). "Purification and partial characterization of a nucleolar scleroderma antigen (Mr = 34,000; pI, 8.5) rich in NG,NG-dimethylarginine". The Journal of Biological Chemistry. 260 (26): 14304–10. PMID2414294.
Méhes G, Pajor L (Jun 1995). "Nucleolin and fibrillarin expression in stimulated lymphocytes and differentiating HL-60 cells. A flow cytometric assay". Cell Proliferation. 28 (6): 329–36. doi:10.1111/j.1365-2184.1995.tb00074.x. PMID7626687.
Magoulas C, Zatsepina OV, Jordan PW, Jordan EG, Fried M (Feb 1998). "The SURF-6 protein is a component of the nucleolar matrix and has a high binding capacity for nucleic acids in vitro". European Journal of Cell Biology. 75 (2): 174–83. doi:10.1016/s0171-9335(98)80059-9. PMID9548374.
Ai LS, Lin CH, Hsieh M, Li C (Oct 1999). "Arginine methylation of a glycine and arginine rich peptide derived from sequences of human FMRP and fibrillarin". Proceedings of the National Science Council, Republic of China. Part B, Life Sciences. 23 (4): 175–80. PMID10518318.
Nicol SM, Causevic M, Prescott AR, Fuller-Pace FV (Jun 2000). "The nuclear DEAD box RNA helicase p68 interacts with the nucleolar protein fibrillarin and colocalizes specifically in nascent nucleoli during telophase". Experimental Cell Research. 257 (2): 272–80. doi:10.1006/excr.2000.4886. PMID10837141.
Pellizzoni L, Baccon J, Charroux B, Dreyfuss G (Jul 2001). "The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1". Current Biology. 11 (14): 1079–88. doi:10.1016/S0960-9822(01)00316-5. PMID11509230.
Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI (Jan 2002). "Directed proteomic analysis of the human nucleolus". Current Biology. 12 (1): 1–11. doi:10.1016/S0960-9822(01)00650-9. PMID11790298.
Cimato TR, Tang J, Xu Y, Guarnaccia C, Herschman HR, Pongor S, Aletta JM (Feb 2002). "Nerve growth factor-mediated increases in protein methylation occur predominantly at type I arginine methylation sites and involve protein arginine methyltransferase 1". Journal of Neuroscience Research. 67 (4): 435–42. doi:10.1002/jnr.10123. PMID11835310.
Herrera-Esparza R, Kruse L, von Essen M, Campos L, Barbosa O, Bollain JJ, Badillo I, Avalos-Díaz E (Oct 2002). "U3 snoRNP associates with fibrillarin a component of the scleroderma clumpy nucleolar domain". Archives of Dermatological Research. 294 (7): 310–7. doi:10.1007/s00403-002-0338-7. PMID12373336.
