Structural basis of archaeal FttA-dependent transcription termination

Linlin You; Chengyuan Wang; Vadim Molodtsov; Konstantin Kuznedelov; Xinyi Miao; Breanna R. Wenck; Paul Ulisse; Travis J. Sanders; Craig J. Marshall; Emre Firlar; Jason T. Kaelber; Thomas J. Santangelo; Richard H. Ebright

doi:10.1038/s41586-024-07979-9

Structural basis of archaeal FttA-dependent transcription termination

Linlin You, Chengyuan Wang, Vadim Molodtsov, Konstantin Kuznedelov, Xinyi Miao, Breanna R. Wenck, Paul Ulisse, Travis J. Sanders, Craig J. Marshall, Emre Firlar, Jason T. Kaelber, Thomas J. Santangelo, Richard H. Ebright

Rutgers, The State University

Research output: Contribution to journal › Article › peer-review

Abstract

The ribonuclease FttA (also known as aCPSF and aCPSF1) mediates factor-dependent transcription termination in archaea^1–3. Here we report the structure of a Thermococcus kodakarensis transcription pre-termination complex comprising FttA, Spt4, Spt5 and a transcription elongation complex (TEC). The structure shows that FttA interacts with the TEC in a manner that enables RNA to proceed directly from the TEC RNA-exit channel to the FttA catalytic centre and that enables endonucleolytic cleavage of RNA by FttA, followed by 5′→3′ exonucleolytic cleavage of RNA by FttA and concomitant 5′→3′ translocation of FttA on RNA, to apply mechanical force to the TEC and trigger termination. The structure further reveals that Spt5 bridges FttA and the TEC, explaining how Spt5 stimulates FttA-dependent termination. The results reveal functional analogy between bacterial and archaeal factor-dependent termination, functional homology between archaeal and eukaryotic factor-dependent termination, and fundamental mechanistic similarities in factor-dependent termination in bacteria, archaea, and eukaryotes.

Original language	American English
Pages (from-to)	229-236
Number of pages	8
Journal	Nature
Volume	635
Issue number	8037
DOIs	https://doi.org/10.1038/s41586-024-07979-9
State	Published - Nov 7 2024

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title = "Structural basis of archaeal FttA-dependent transcription termination",

abstract = "The ribonuclease FttA (also known as aCPSF and aCPSF1) mediates factor-dependent transcription termination in archaea1–3. Here we report the structure of a Thermococcus kodakarensis transcription pre-termination complex comprising FttA, Spt4, Spt5 and a transcription elongation complex (TEC). The structure shows that FttA interacts with the TEC in a manner that enables RNA to proceed directly from the TEC RNA-exit channel to the FttA catalytic centre and that enables endonucleolytic cleavage of RNA by FttA, followed by 5′→3′ exonucleolytic cleavage of RNA by FttA and concomitant 5′→3′ translocation of FttA on RNA, to apply mechanical force to the TEC and trigger termination. The structure further reveals that Spt5 bridges FttA and the TEC, explaining how Spt5 stimulates FttA-dependent termination. The results reveal functional analogy between bacterial and archaeal factor-dependent termination, functional homology between archaeal and eukaryotic factor-dependent termination, and fundamental mechanistic similarities in factor-dependent termination in bacteria, archaea, and eukaryotes.",

author = "Linlin You and Chengyuan Wang and Vadim Molodtsov and Konstantin Kuznedelov and Xinyi Miao and Wenck, {Breanna R.} and Paul Ulisse and Sanders, {Travis J.} and Marshall, {Craig J.} and Emre Firlar and Kaelber, {Jason T.} and Santangelo, {Thomas J.} and Ebright, {Richard H.}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2024.",

year = "2024",

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doi = "10.1038/s41586-024-07979-9",

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T1 - Structural basis of archaeal FttA-dependent transcription termination

AU - You, Linlin

AU - Wang, Chengyuan

AU - Molodtsov, Vadim

AU - Kuznedelov, Konstantin

AU - Miao, Xinyi

AU - Wenck, Breanna R.

AU - Ulisse, Paul

AU - Sanders, Travis J.

AU - Marshall, Craig J.

AU - Firlar, Emre

AU - Kaelber, Jason T.

AU - Santangelo, Thomas J.

AU - Ebright, Richard H.

PY - 2024/11/7

Y1 - 2024/11/7

N2 - The ribonuclease FttA (also known as aCPSF and aCPSF1) mediates factor-dependent transcription termination in archaea1–3. Here we report the structure of a Thermococcus kodakarensis transcription pre-termination complex comprising FttA, Spt4, Spt5 and a transcription elongation complex (TEC). The structure shows that FttA interacts with the TEC in a manner that enables RNA to proceed directly from the TEC RNA-exit channel to the FttA catalytic centre and that enables endonucleolytic cleavage of RNA by FttA, followed by 5′→3′ exonucleolytic cleavage of RNA by FttA and concomitant 5′→3′ translocation of FttA on RNA, to apply mechanical force to the TEC and trigger termination. The structure further reveals that Spt5 bridges FttA and the TEC, explaining how Spt5 stimulates FttA-dependent termination. The results reveal functional analogy between bacterial and archaeal factor-dependent termination, functional homology between archaeal and eukaryotic factor-dependent termination, and fundamental mechanistic similarities in factor-dependent termination in bacteria, archaea, and eukaryotes.

AB - The ribonuclease FttA (also known as aCPSF and aCPSF1) mediates factor-dependent transcription termination in archaea1–3. Here we report the structure of a Thermococcus kodakarensis transcription pre-termination complex comprising FttA, Spt4, Spt5 and a transcription elongation complex (TEC). The structure shows that FttA interacts with the TEC in a manner that enables RNA to proceed directly from the TEC RNA-exit channel to the FttA catalytic centre and that enables endonucleolytic cleavage of RNA by FttA, followed by 5′→3′ exonucleolytic cleavage of RNA by FttA and concomitant 5′→3′ translocation of FttA on RNA, to apply mechanical force to the TEC and trigger termination. The structure further reveals that Spt5 bridges FttA and the TEC, explaining how Spt5 stimulates FttA-dependent termination. The results reveal functional analogy between bacterial and archaeal factor-dependent termination, functional homology between archaeal and eukaryotic factor-dependent termination, and fundamental mechanistic similarities in factor-dependent termination in bacteria, archaea, and eukaryotes.

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Structural basis of archaeal FttA-dependent transcription termination

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