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Allosteric transcription stimulation by super elongation complex

ABSTRACT: The super elongation complex (SEC) contains the positive transcription elongation factor b (P-TEFb) and a subcomplex, ELL2-EAF1, which stimulates transcription elongation by RNA polymerase II (Pol II). Here we report the cryo-EM structure of ELL2-EAF1 bound to a Pol II elongation complex at 2.8 Å resolution. The ELL2-EAF1 dimerization module directly binds the Pol II lobe, explaining how SEC delivers P-TEFb to Pol II. The same site on the lobe also binds the initiation factor TFIIF, consistent with SEC binding only after the transition from transcription initiation to elongation. Structure-guided functional analysis shows that elongation stimulation requires the dimerization module and an ELL2 protein linker that tethers this module to the Pol II protrusion. Our results show that SEC stimulates elongation allosterically and indicate that this stimulation involves stabilization of a further closed conformation of the Pol II active center cleft.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human) Sus Scrofa Domesticus (domestic Pig)

SUBMITTER: Momchil Ninov

LAB HEAD: Henning Urlaub

PROVIDER: PXD024457 | Pride | 2021-07-15

REPOSITORIES: Pride

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Targeting Processive Transcription Elongation via SEC Disruption for MYC-Induced Cancer Therapy

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