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Structure paper

TitleStructural insights into human co-transcriptional capping.
Journal, issue, pagesMol Cell, Vol. 83, Issue 14, Page 2464-22477.e5, Year 2023
Publish dateJun 21, 2023
AuthorsGaurika Garg / Christian Dienemann / Lucas Farnung / Juliane Schwarz / Andreas Linden / Henning Urlaub / Patrick Cramer /
PubMed AbstractCo-transcriptional capping of the nascent pre-mRNA 5' end prevents degradation of RNA polymerase (Pol) II transcripts and suppresses the innate immune response. Here, we provide mechanistic insights ...Co-transcriptional capping of the nascent pre-mRNA 5' end prevents degradation of RNA polymerase (Pol) II transcripts and suppresses the innate immune response. Here, we provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryoelectron microscopy (cryo-EM) structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end. Addition of a GMP moiety can occur when the RNA is ∼22 nt long, sufficient to reach the active site of the guanylyltransferase. For subsequent cap(1) methylation, the methyltransferase CMTR1 binds the Pol II stalk and can receive RNA after it is grown to ∼29 nt in length. The observed rearrangements of capping factors on the Pol II surface may be triggered by the completion of catalytic reaction steps and are accommodated by domain movements in the elongation factor DRB sensitivity-inducing factor (DSIF).
External linksMol Cell / PubMed:37369200
MethodsEM (single particle)
Resolution3.2 - 4.0 Å
Structure data

17403

8p4a

EMDB-17403, PDB-8p4a:
Structural insights into human co-transcriptional capping - structure 1
Method: EM (single particle) / Resolution: 3.6 Å

17404

8p4b

EMDB-17404, PDB-8p4b:
Structural insights into human co-transcriptional capping - structure 2
Method: EM (single particle) / Resolution: 3.2 Å

17405

8p4c

EMDB-17405, PDB-8p4c:
Structural insights into human co-transcriptional capping - structure 3
Method: EM (single particle) / Resolution: 3.8 Å

17406

8p4d

EMDB-17406, PDB-8p4d:
Structural insights into human co-transcriptional capping - structure 4
Method: EM (single particle) / Resolution: 3.6 Å

17407

8p4e

EMDB-17407, PDB-8p4e:
Structural insights into human co-transcriptional capping - structure 5
Method: EM (single particle) / Resolution: 3.9 Å

17408

8p4f

EMDB-17408, PDB-8p4f:
Structural insights into human co-transcriptional capping - structure 6
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-MGT:
7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE

ChemComp-SAM:
S-ADENOSYLMETHIONINE / S-Adenosyl methionine

Source
  • homo sapiens (human)
  • sus scrofa (pig)
  • unidentified (others)
  • pig (pig)
  • synthetic construct (others)
KeywordsTRANSCRIPTION / rna polymerase II / capping

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