Abstract
The yeast and mammalian branchpoint sequence binding
proteins (BBP and mBBP/SF1) contain both KH domain and
Zn knuckle RNA-binding motifs. The single KH domain of
these proteins is sufficient for specific recognition of
the pre-mRNA branchpoint sequence (BPS). However, an interaction
is only apparent if one or more accessory modules are present
to increase binding affinity. The Zn knuckles of BBP/mBBP
can be replaced by an RNA-binding peptide derived from
the HIV-1 nucleocapsid protein or by an arginine-serine
(RS)7 peptide, without loss of specificity.
Only the seven-nucleotide branchpoint sequence and two
nucleotides to either side are necessary for RNA binding
to the chimeric proteins. Therefore, we propose that all
three of these accessory RNA-binding modules bind the phosphate
backbone, whereas the KH domain interacts specifically
with the bases of the BPS. Proteins and protein complexes
with multiple RNA-binding motifs are frequent, suggesting
that an intimate collaboration between two or more motifs
will be a general theme in RNA–protein interactions.