Identification, structure, and functional requirement of the Mediator submodule Med7N/31
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Published on: September 26, 2018
Tobias Koschubs1, Martin Seizl, Laurent Larivière
1Gene Center and Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.
Abstract:
Mediator is a modular multiprotein complex required for regulated transcription by RNA polymerase (Pol) II. Here, we show that the middle module of the Mediator core contains a submodule of unique structure and function that comprises the N-terminal part of subunit Med7 (Med7N) and the highly conserved subunit Med31 (Soh1). The Med7N/31 submodule shows a conserved novel fold, with two proline-rich stretches in Med7N wrapping around the right-handed four-helix bundle of Med31. In vitro, Med7N/31 is required for activated transcription and can act in trans when added exogenously. In vivo, Med7N/31 has a predominantly positive function on the expression of a specific subset of genes, including genes involved in methionine metabolism and iron transport. Comparative phenotyping and transcriptome profiling identify specific and overlapping functions of different Mediator submodules.
Insights
Researchers discovered a new submodule within the Mediator complex, essential for gene transcription. This Med7N/31 submodule plays a crucial role in regulating gene expression, particularly for genes involved in methionine metabolism and iron transport.
Area of Science:
- Molecular Biology
- Gene Regulation
Background:
- Mediator is a crucial multiprotein complex for regulated transcription by RNA polymerase II.
- Understanding Mediator's modular structure is key to deciphering gene expression control.
Purpose of the Study:
- To investigate the structure and function of a novel submodule within the Mediator complex.
- To elucidate the role of the Med7N/31 submodule in gene transcription and cellular processes.
Main Methods:
- Structural analysis of the Med7N/31 submodule.
- In vitro transcription assays.
- In vivo functional studies including comparative phenotyping and transcriptome profiling.
Main Results:
- Identified a unique Med7N/31 submodule with a conserved novel fold.
- Demonstrated Med7N/31's requirement for activated transcription in vitro and its ability to act in trans.
- Showed Med7N/31 positively regulates specific genes, including those in methionine metabolism and iron transport pathways in vivo.
Conclusions:
- The Med7N/31 submodule possesses unique structural and functional properties critical for Mediator complex activity.
- This submodule plays a significant role in regulating specific gene expression programs essential for cellular function.
- Comparative analysis reveals distinct and shared functions among Mediator submodules, offering insights into transcriptional regulation complexity.
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