Abstract
Regulation of transcription elongation by RNA polymerase II (Pol II) is a key regulatory step in gene transcription. Recently, the little elongation complex (LEC)-which contains the transcription elongation factor ELL/EAF-was found to be required for the transcription of Pol II-dependent small nuclear RNA (snRNA) genes. Here we show that the human Mediator subunit MED26 plays a role in the recruitment of LEC to a subset of snRNA genes through direct interaction of EAF and the N-terminal domain (NTD) of MED26. Loss of MED26 in cells decreases the occupancy of LEC at a subset of snRNA genes and results in a reduction in their transcription. Our results suggest that the MED26-NTD functions as a molecular switch in the exchange of TBP-associated factor 7 (TAF7) for LEC to facilitate the transition from initiation to elongation during transcription of a subset of snRNA genes.
Highlights
Regulation of transcription elongation by RNA polymerase II (Pol II) is a key regulatory step in gene transcription
Mediator purified through FLAG-MED26-wt or MED26-CS was copurified with Pol II and Mediator components; deletion of MED26-N-terminal domain (NTD) resulted in loss of Mediator interaction with little elongation complex (LEC) components, ICE1 (KIAA0947), eleven-nineteen lysine-rich leukaemia (ELL) and EAF1 (Fig. 1a)
Since we previously showed that substitution of two amino-acid residues R61 and K62 of MED26-NTD with A interferes with both direct interaction with ELL-associated factors (EAFs) and interaction with the components of super elongation complex (SEC) in cells[20], we tested whether the same substitution interferes with the interaction of MED26-NTD and LEC in cells
Summary
Regulation of transcription elongation by RNA polymerase II (Pol II) is a key regulatory step in gene transcription. The little elongation complex (LEC)—which contains the transcription elongation factor ELL/EAF—was found to be required for the transcription of Pol II-dependent small nuclear RNA (snRNA) genes. We show that the human Mediator subunit MED26 plays a role in the recruitment of LEC to a subset of snRNA genes through direct interaction of EAF and the N-terminal domain (NTD) of MED26. Transcription of Pol II-transcribed snRNA genes requires an integrator complex that binds to the Ser7-phosphorylated form of the Pol II C-terminal domain (CTD) and proceeds to the 30 end formation[16,17]. It has been shown that Mediator is involved in the activation of transcription of a number of Pol II-dependent genes at multiple steps, including pre-initiation, promoter clearance, transcription elongation, transcription termination and mRNA splicing steps[20,21,22,23,24]. Generality of the role of MED26 in recruiting ELL/EAF-containing complexes has not been established
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