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Structure paper

TitleStructural basis of long-range transcription-translation coupling.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 123, Issue 24, Page e2528970123, Year 2026
Publish dateJun 16, 2026
AuthorsChengyuan Wang / Vadim Molodtsov / Shashank Shandilya / Linlin You / Jing Zhang / Konstantin Kuznedelov / Bryce E Nickels / Jason T Kaelber / Gregor Blaha / Richard H Ebright /
PubMed AbstractStructures recently have been reported of molecular assemblies that mediate transcription-translation coupling in . In these molecular assemblies, termed "coupled transcription-translation complexes" ...Structures recently have been reported of molecular assemblies that mediate transcription-translation coupling in . In these molecular assemblies, termed "coupled transcription-translation complexes" or "TTC-B," RNA polymerase (RNAP) directly interacts with the ribosome, the transcription elongation factor NusG or its paralog RfaH forms a bridge between RNAP and ribosome, and the transcription elongation factor NusA optionally forms a second bridge between RNAP and ribosome. Here, we report structures of coupled transcription-translation complexes having mRNA spacers between RNAP and ribosome longer than the maximum-length mRNA spacer compatible with formation of TTC-B. The results define a class of coupled transcription-translation complex, termed "TTC-LC," where "LC" denotes "long-range coupling." TTC-LC differs from TTC-B by a ~60° rotation and ~70 Å translation of RNAP relative to ribosome, resulting in loss of direct interactions between RNAP and ribosome and creation of a ~70 Å gap between RNAP and ribosome. TTC-LC accommodates long mRNA spacers by looping out mRNA from the gap between RNAP and ribosome. We present evidence that TTC-LC is a functional intermediate in assembling and disassembling TTC-B, mediating pre-TTC-B transcription-translation coupling before a ribosome catches up to RNAP, and mediating post-TTC-B transcription-translation coupling after a ribosome stops moving and RNAP continues moving. We show that TTC-B, but not TTC-LC, is severely defective in RNA-hairpin-dependent transcription termination, and that both TTC-B and TTC-LC are severely defective in Rho-dependent transcription termination.
External linksProc Natl Acad Sci U S A / PubMed:42268877 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 9.3 Å
Structure data

EMDB-43332, PDB-8vkv:
Escherichia coli transcription-translation coupled complex (TTC-B) containing mRNA with a 33 nt long spacer, ops signal, RfaH, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-43335, PDB-8vl1:
Escherichia coli transcription-translation loosely coupled complex (TTC-LC) containing mRNA with a 36 nt long spacer, ops signal, RfaH, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 5.3 Å

EMDB-43387, PDB-8voo:
Escherichia coli transcription-translation loosely coupled complex (TTC-LC) containing mRNA with a 39 nt long spacer, ops signal, RfaH, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-43388, PDB-8vop:
Escherichia coli transcription-translation coupled complex (TTC-B) containing mRNA with a 36 nt long spacer, NusG, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 6.0 Å

EMDB-43389, PDB-8voq:
Escherichia coli transcription-translation loosely coupled complex (TTC-LC) containing mRNA with a 39 nt long spacer, NusG, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 9.3 Å

EMDB-43390, PDB-8vor:
Escherichia coli transcription-translation loosely coupled complex (TTC-LC) containing mRNA with a 51 nt long spacer, NusG, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-43391, PDB-8vos:
Escherichia coli transcription-translation loosely coupled complex (TTC-LC) containing mRNA with a 60 nt long spacer, NusG, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-72553: Escherichia coli transcription-translation loosely coupled complex (TTC-LC^walked) containing mRNA with a 39 nt long spacer, NusG, NusA, and fMet-tRNAs in E-site and P-site - Map 1a
Method: EM (single particle) / Resolution: 8.5 Å

EMDB-72554: Escherichia coli transcription-translation loosely coupled complex complex (TTC-LC^walked) containing mRNA with a 39 nt long spacer, NusG, NusA, and fMet-tRNAs in E-site and P-site - Map 1
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-72646, PDB-9y79:
Escherichia coli transcription-translation loosely coupled complex (TTC-LC^walked) containing mRNA with a 39 nt long spacer, NusG, NusA, and fMet-tRNAs in E-site and P-site
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • escherichia coli (E. coli)
  • synthetic construct (others)
KeywordsTRANSCRIPTION / translation / coupling / RfaH / NusA / ops / TTC / NusG / RIBOSOME/TRANSFERASE/DNA/RNA / Transcription-translation coupled complex / RIBOSOME-TRANSFERASE-DNA-RNA complex

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