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Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events
Published on: May 13, 2019
Conformational toggle triggers a modulator of RNA polymerase activity
Padraig Deighan1, Ann Hochschild
1Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Trends in Biochemical Sciences
|July 4, 2006
Summary
Newly discovered transcription factors, like Gfh1, regulate RNA polymerase (RNAP) activity. Crystal structures reveal conformational differences between Gfh1 and GreA, with pH-dependent changes offering a potential explanation for Gfh1
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Transcription factors modulate RNA polymerase (RNAP) activity.
- Gre factors are known to stimulate RNAP transcript cleavage.
- A newly identified homolog, Gfh1, inhibits RNAP catalytic functions.
Purpose of the Study:
- To determine the crystal structures of Gfh1.
- To investigate the structural relationship between Gfh1 and GreA.
- To understand the mechanism of Gfh1-mediated RNAP inhibition.
Main Methods:
- X-ray crystallography to obtain high-resolution structures of Gfh1.
- Comparative structural analysis of Gfh1 and GreA.
- Biochemical assays to assess Gfh1 activity under varying pH conditions.
Main Results:
- Three crystal structures of Gfh1 were determined, revealing its inhibitory role.
- A significant conformational discrepancy exists between Gfh1 and GreA.
- Gfh1 activity is modulated by a pH-dependent conformational switch.
Conclusions:
- Gfh1 represents a novel class of RNAP inhibitors.
- The structural differences between Gfh1 and GreA highlight distinct regulatory mechanisms.
- pH-dependent conformational changes offer a potential mechanism for regulating Gfh1 activity and RNAP function.
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