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Transcriptional elongation involves dynamic interactions among RNA polymerase
and single-stranded and double-stranded nucleic acids in the ternary complex. In
prokaryotes its regulation provides an important mechanism of genetic control.
Analogous eukaryotic mechanisms are not well understood, but may control
expression of proto-oncogenes and viruses, including the human immunodeficiency
virus HIV-1 (ref. 8). The highly conserved eukaryotic transcriptional elongation
factor TFIIS enables RNA polymerase II (RNAPII) to read though pause or
termination sites, nucleosomes and sequence-specific DNA-binding proteins. Two
distinct domains of human TFIIS, which bind RNAPII and nucleic acids, regulate
read-through and possibly nascent transcript cleavage. Here we describe the
three-dimensional NMR structure of a Cys4 nucleic-acid-binding domain from human
TFIIS. Unlike previously characterized zinc modules, which contain an
alpha-helix, this structure consists of a three-stranded beta-sheet. Analogous
Cys4 structural motifs may occur in other proteins involved in DNA or RNA
transactions, including RNAPII itself. This new structure, designated the Zn
ribbon, extends the repertoire of Zn-mediated peptide architectures and
highlights the growing recognition of the beta-sheet as a motif of nucleic-acid
recognition.
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