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by the epidermal growth factor receptor is atten- 
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267:7967-7970. 
RIBONUCLEOPROTEIN COMPLEXES OF HETEROGENEOUS NUCLEAR RNA, 
NUCLEAR STRUCTURES, AND MESSENGER RNA FORMATION 
Gideon Dreyfuss, Ph.D., Investigator 
Messenger RNAs (mRNAs) are formed in the 
nuclei of eukaryotic cells by extensive post- 
transcriptional processing of primary transcripts of 
protein-coding genes. These transcripts, called het- 
erogeneous nuclear RNAs (hnRNAs) or pre-mRNAs, 
are produced by RNA polymerase II. From the time 
hnRNAs emerge from the transcription complex, 
and throughout the time they are in the nucleus, 
they are associated with proteins. The collective 
term for the proteins that bind hnRNAs and that are 
not stable components of other classes of RNP com- 
plexes, such as snRNPs, is hnRNPs. The full range of 
functions and the mechanism of action of hnRNPs 
are not known. It can be anticipated, however, that 
hnRNPs influence the structure of hnRNAs and facili- 
tate or hinder the interaction of hnRNA sequences 
with other components that are needed for pre- 
mRNA processing. The hnRNPs may also play impor- 
tant roles in the interaction of hnRNA with other 
nuclear structures, in nucleocytoplasmic transport 
of mRNA, and in other cellular processes. They are 
also major nuclear structures. In addtion, what has 
been learned from the study of hnRNPs turned out 
to be extremely instructive for other RNA-binding 
proteins, including those that control developmen- 
tally important pathways, snRNPs and mRNA-bind- 
ing proteins (mRNPs). 
hnRNP Complexes 
Photochemical RNA-protein crosslinking in intact 
cells and affinity chromatography methods have 
been used to identify and purify the major hnRNPs 
and mRNPs of vertebrate cells, and monoclonal anti- 
bodies to many of them have been produced. These 
antibodies were used to develop an immunopurifi- 
cation procedure for hnRNP complexes and to be- 
gin the characterization of these proteins. 
The most detailed picture of the protein composi- 
tion of hnRNP complexes is presently available for 
human cells. Considerable information is also be- 
coming available for invertebrates, particularly Dro- 
sophila melanogaster. Human hnRNP complexes 
contain large hnRNA (>10 kb) and at least 20 major 
proteins, designated A-U, in the range of 34-120 
kDa. The arrangement of the proteins on specific 
hnRNAs, which is probably important in determin- 
ing the structure of the hnRNA, is one of the areas on 
which much work is focused. Several hnRNPs were 
found to have RNA-binding specificities. Some of 
the specificities of the major hnRNPs are for se- 
quences that are important for pre-mRNA process- 
ing and polyadenylation, and these binding prefer- 
ences are probably directly related to roles for these 
proteins in mRNA formation. Dr. Dreyfuss's labora- 
tory previously described the isolation and sequenc- 
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