Autoantibodies and Autoimmunity
471
Tab. 3
Examples of the function of nuclear autoantigens and the effects of autoantibody on antigen
function.
Autoantigen
Function
Autoantibody effect
a
Known function
Sm/nRNP (U1, 2, 4–6 snRNP)
Pre-mRNA splicing
Inhibition of pre-mRNA
splicing
PCNA (DNA polymerase delta
auxiliary protein)
DNA replication
Inhibition of DNA replication
and repair
RNA polymerase I
Transcription of rRNA
Inhibition of rRNA
transcription
tRNA polymerase
Aminoacylation of tRNA
Inhibition of charging of tRNA
Ribosomal RNP
mRNA translation
Inhibition of protein synthesis
Centromere/kinetochore
Microtubule-based
chromosome movement
during mitosis
Inhibition of centromere
formation and function
Probable function
Fibrillarin (Box C/D snoRNP)
Processing and methylation of
pre-rRNA
Blocks translocation of
±brillarin during the cell
cycle, thereby influencing
the ultrastructure of the
nucleolus.
NOR-90
Nucleolar transcription factor
Not tested
a
Inhibition of function has been demonstrated
in vitro
or following injection of autoantibody into
living cells.
the use of autoantibodies that identify spe-
ciFc components of such complexes has
aided in identifying other subunits of these
complexes, with profound consequences.
Thus, the initial identiFcation of anti-Sm
and anti-nRNP autoantibodies in SLE led
to the observation that they recognize some
of the protein components of the snRNP
particles, fueling subsequent studies that
showed the snRNPs as components of the
spliceosome complex that functions in pre-
mRNA splicing.
As the functional associations of au-
toantigens have become known, attempts
to uncover the role of the autoantigen it-
self have revealed that autoantibodies can
directly inhibit the function of their target
autoantigen (Table 3). Although it remains
to be determined, it seems likely that such
inhibition reflects the involvement of a
conserved protein sequence or structure
in functional activity. An increasing num-
ber of autoantibodies, many of unknown
molecular speciFcity, recognize their au-
toantigen only in a particular functional
state or phase of the cell cycle. Of the
several examples known, the best charac-
terized is PCNA, which is the auxiliary
protein of DNA polymerase delta and is
recognized by autoantibodies only during
mitosis, even though PCNA is present
throughout the cell cycle. When a popu-
lation of cells at different stages of the
cell cycle is used as substrate in the II±
test, anti-PCNA autoantibodies produce
varying degrees of fluorescence intensity,
being negative for G
0
cells and highly
positive for S-phase cells (±ig. 3c). These
previous page 471 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 473 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off