Autoantibody Probes for Mammalian Gene Expression 
snRNPs that are closely related to the splicing 
snRNPs. One is the U7 snRNP, which is only 
1/1,000 as abundant as the splicing snRNPs. We 
have recently demonstrated that it participates in 
forming the 3' ends of histone mRNAs by using 
base-pairing to recognize a specific sequence in 
the pre-mRNA just downstream of the cut site. 
Other related low-abundance snRNPs, which we 
anticipate all function in some aspect of mRNA 
metabolism, include viral snRNPs. For instance, 
in marmoset cells infected by Herpesvirus sai- 
miri, which causes malignant transformation of 
the T cells of the immune system, there are five 
small RNAs encoded by the viral genome. They 
are hypothesized to contribute to either mRNA 
processing or stabilization, thereby enhancing 
the process of cellular transformation. 
Another type of patient autoantibody is di- 
rected against a different class of small RNPs lo- 
calized in the nucleolus, where ribosomal RNA 
processing and ribosome assembly occur. Re- 
cently, in collaboration with Barbara Sollner- 
Webb's laboratory at the Johns Hopkins Univer- 
sity School of Medicine, we established that the 
most abundant nucleolar snRNP (containing U3 
RNA) is essential for the first step of ribosomal 
RNA processing. The possibility that other nu- 
cleolar snRNPs act in subsequent steps is now be- 
ing investigated. A separate study is designed to 
dissect the signals that dictate the delivery of 
these snRNPs to their nucleolar site of action. 
Yet another autoantibody type precipitates 
EBERs, two small RNAs specified by Epstein-Barr 
virus (EBV), the causative agent of infectious 
mononucleosis and also implicated in several hu- 
man cancers. Since EBERs are among the few viral 
products that are expressed in EBV-transformed 
cells, they must be important to the induction or 
maintenance of the transformed state. We have 
recently discovered a highly abundant, highly 
conserved cell protein that binds the EBERs and 
hope that its characterization will lead us to an 
elucidation of EBER function. 
Finally, we are studying the enzyme telomer- 
ase, which synthesizes the ends of chromosomes 
of all higher organisms. In the unicellular ciliate 
Tetrahymena, telomerase has been shown to be 
an RNP. We have demonstrated telomerase activ- 
ity in mammalian cell extracts and are now seek- 
ing to identify the mammalian snRNP. It ap- 
pears to be responsible for the "healing" of bro- 
ken chromosomes, as exemplified by certain 
thalassemias. 
Thus autoantibodies are potent probes for de- 
ciphering some of the fundamental reactions oc- 
curring in all mammalian cells, those involved in 
gene expression. Characterization of new cellu- 
lar particles like snRNPs is significant for future 
studies of basic cellular processes and how they 
might be altered by disease. Furthermore, our re- 
search has provided new ways of diagnosing pa- 
tient autoantibodies, which are helpful in the 
diagnosis and treatment of diseases like SLE. 
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