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TitleAllosteric transcription stimulation by RNA polymerase II super elongation complex.
Journal, issue, pagesMol Cell, Vol. 81, Issue 16, Page 3386-3399.e10, Year 2021
Publish dateAug 19, 2021
AuthorsYing Chen / Seychelle M Vos / Christian Dienemann / Momchil Ninov / Henning Urlaub / Patrick Cramer /
PubMed AbstractThe super elongation complex (SEC) contains the positive transcription elongation factor b (P-TEFb) and the subcomplex ELL2-EAF1, which stimulates RNA polymerase II (RNA Pol II) elongation. Here, we ...The super elongation complex (SEC) contains the positive transcription elongation factor b (P-TEFb) and the subcomplex ELL2-EAF1, which stimulates RNA polymerase II (RNA Pol II) elongation. Here, we report the cryoelectron microscopy (cryo-EM) structure of ELL2-EAF1 bound to a RNA Pol II elongation complex at 2.8 Å resolution. The ELL2-EAF1 dimerization module directly binds the RNA Pol II lobe domain, explaining how SEC delivers P-TEFb to RNA 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 the stimulation of RNA elongation requires the dimerization module and the ELL2 linker that tethers the module to the RNA Pol II protrusion. Our results show that SEC stimulates elongation allosterically and indicate that this stimulation involves stabilization of a closed conformation of the RNA Pol II active center cleft.
External linksMol Cell / PubMed:34265249
MethodsEM (single particle)
Resolution2.8 - 4.14 Å
Structure data

EMDB-12966:
Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1 Map 5, Focused map for ELL2-EAF1 region
Method: EM (single particle) / Resolution: 3.25 Å

EMDB-12967:
Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1, Map 6, Focused map for the stalk of Pol II
Method: EM (single particle) / Resolution: 3.28 Å

EMDB-12968:
Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1, Map 7, Focused map for Pol II core
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-12969: Structure of active transcription elongation complex Pol II-DSIF (SPT5-KOW5)-ELL2-EAF1, Composite map 1 (Primary map)
PDB-7okx: Structure of active transcription elongation complex Pol II-DSIF (SPT5-KOW5)-ELL2-EAF1 (composite structure)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-12970:
Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1, Map 8, Global map used to fit upstream DNA
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-12971:
Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1, Map 9, Global map used to fit SPT4-SPT5-NGN
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-12972:
Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1, Map 10, Global map used to fit SPT5-KOW2-3-KOWX-4
Method: EM (single particle) / Resolution: 4.14 Å

EMDB-12973: Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1, composite map 2
PDB-7oky: Structure of active transcription elongation complex Pol II-DSIF-ELL2-EAF1(composite structure)
Method: EM (single particle) / Resolution: 4.14 Å

EMDB-12974: Structure of active transcription elongation complex Pol II-DSIF (SPT5-KOW5) alone, Map 11, Global map
PDB-7ol0: Structure of active transcription elongation complex Pol II-DSIF (SPT5-KOW5)
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • sus scrofa (pig)
  • homo sapiens (human)
  • hiv whole-genome vector aa1305#18 (others)
  • Pig (pig)
KeywordsTRANSCRIPTION / Pol II / Super elongation complex / ELL2 / EAF1

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