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Aberrant antibodies, which are produced by individuals with certain autoimmune diseases, bind to small nuclear ribonucleoprotein particles (snRNPs)
Update time:2019-01-09 00:40:25   【 Font: Large  Medium Small

    Although it might seem that only a few specific endonucleases and a ligase might suffice to catalyze splicing reactions, eukaryotic cells use a very sophisticated piece of machinery to carry out the steps involved in splicing. As often happens in science, the first clue to the nature of this machinery came from studies in a seemingly unrelated field. People suffering from autoimmune diseases known as mixed connective tissue disease and systemic lupus erythematosus make aberrant antibodies that attack components of their own cells. One such antibody, called the anti-Smith or anti-Sm antibody, binds to small ribonucleoprotein particles in the cell nucleus. Joan Steitz and coworkers suspected that these small ribonucleoproteins might help to process pre-mRNA and set about isolating them so that they could study their function(s). The isolation method they devised was to first tag the ribonucleoprotein particles in a human cell extract with antibodies from the serum of a lupus patient and then pull the tagged ribonucleoproteins out of the extract with an insoluble Stapbylococcus aureus cell wall preparation that binds to antibodies. When Steitz and coworkers analyzed RNA molecules that had been extracted from the ribonucleoprotein particles by polyacrylamide gel electrophoresis, they observed discrete bands corresponding to RNA molecules with chain lengths between 100 and 200 nucleotides long. Because each of the small nuclear RNA molecules is uridine-rich, they are called U1 snRNA, U2 snRNA, U4 snRNA, U5 snRNA, and U6 snRNA. The reason that there is no U3 snRNA is that the lupus antibodies do not bind to the ribonucleoprotein that contains this RNA. U3 snRNA is involved with rRNA rather than mRNA formation. The U1, U2, U4, and U5 snRNAs each has a 2, 2, 7 trimethyl guanosine cap at its 5'-end while U6 has a ?-methyl phosphate cap.
    Each snRNA is present in its own small nuclear ribonucleoprotein particle (snRNP; or 'snurp' for short). The snRNPs are named U1 snRNP, U2 snRNP, U4 snRNP, U5 snRNP, and U6 snRNP after their snRNA component. U4, U5, and U6 snRNps combine to form a U4/U6 · U5 tri-snRNp particle, which is stabilized by extensive base pairing between U4 and U6 snRNAs and protein-protein interactions between U5 snRNP and the U4/U6 di-snRNP. Although all eukaryotes have the same five kinds of ribonucleoproteins, snRNP concentrations vary from organism to organism. Thus, mamalian cells have approximately 105 to 106 copies of each snRNP, whereas yeast cells have about 100 to 200 copies of each kind.

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