Structure of an active human histone pre-mRNA 3′-end processing machinery

Yadong Sun; Yixiao Zhang; Wei Shen Aik; Xiao Cui Yang; William F. Marzluff; Thomas Walz; Zbigniew Dominski; Liang Tong

doi:10.1126/science.aaz7758

Structure of an active human histone pre-mRNA 3′-end processing machinery

Yadong Sun, Yixiao Zhang, Wei Shen Aik, Xiao Cui Yang, William F. Marzluff, Thomas Walz^*, Zbigniew Dominski^*, Liang Tong^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Journal article › peer-review

72 Citations (Scopus)

Abstract

The 3′-end processing machinery for metazoan replication-dependent histone precursor messenger RNAs (pre-mRNAs) contains the U7 small nuclear ribonucleoprotein and shares the key cleavage module with the canonical cleavage and polyadenylation machinery. We reconstituted an active human histone pre-mRNA processing machinery using 13 recombinant proteins and two RNAs and determined its structure by cryo–electron microscopy. The overall structure is highly asymmetrical and resembles an amphora with one long handle. We captured the pre-mRNA in the active site of the endonuclease, the 73-kilodalton subunit of the cleavage and polyadenylation specificity factor, poised for cleavage. The endonuclease and the entire cleavage module undergo extensive rearrangements for activation, triggered through the recognition of the duplex between the authentic pre-mRNA and U7 small nuclear RNA (snRNA). Our study also has notable implications for understanding canonical and snRNA 3′-end processing.

Original language	English
Pages (from-to)	700-703
Number of pages	4
Journal	Science
Volume	367
Issue number	6478
DOIs	https://doi.org/10.1126/science.aaz7758
Publication status	Published - 7 Feb 2020

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title = "Structure of an active human histone pre-mRNA 3′-end processing machinery",

abstract = "The 3′-end processing machinery for metazoan replication-dependent histone precursor messenger RNAs (pre-mRNAs) contains the U7 small nuclear ribonucleoprotein and shares the key cleavage module with the canonical cleavage and polyadenylation machinery. We reconstituted an active human histone pre-mRNA processing machinery using 13 recombinant proteins and two RNAs and determined its structure by cryo–electron microscopy. The overall structure is highly asymmetrical and resembles an amphora with one long handle. We captured the pre-mRNA in the active site of the endonuclease, the 73-kilodalton subunit of the cleavage and polyadenylation specificity factor, poised for cleavage. The endonuclease and the entire cleavage module undergo extensive rearrangements for activation, triggered through the recognition of the duplex between the authentic pre-mRNA and U7 small nuclear RNA (snRNA). Our study also has notable implications for understanding canonical and snRNA 3′-end processing.",

author = "Yadong Sun and Yixiao Zhang and Aik, {Wei Shen} and Yang, {Xiao Cui} and Marzluff, {William F.} and Thomas Walz and Zbigniew Dominski and Liang Tong",

note = "Funding Information: This research was supported by NIH grants R35GM118093 (to L.T.) and R01GM029832 (to W.F.M. and Z.D.). W.S.A. was also supported by a fellowship from the Raymond and Beverley Sackler Center for Research at Convergence of Disciplines at Columbia University Medical Center. The Simons Electron Microscopy Center at the New York Structural Biology Center is supported by grants from the Simons Foundation (349247), NYSTAR, NIH (GM103310, S10 OD019994), and Agouron Institute (F00316). Publisher copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

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language = "English",

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AU - Sun, Yadong

AU - Zhang, Yixiao

AU - Aik, Wei Shen

AU - Yang, Xiao Cui

AU - Marzluff, William F.

AU - Walz, Thomas

AU - Dominski, Zbigniew

AU - Tong, Liang

N1 - Funding Information: This research was supported by NIH grants R35GM118093 (to L.T.) and R01GM029832 (to W.F.M. and Z.D.). W.S.A. was also supported by a fellowship from the Raymond and Beverley Sackler Center for Research at Convergence of Disciplines at Columbia University Medical Center. The Simons Electron Microscopy Center at the New York Structural Biology Center is supported by grants from the Simons Foundation (349247), NYSTAR, NIH (GM103310, S10 OD019994), and Agouron Institute (F00316). Publisher copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2020/2/7

Y1 - 2020/2/7

N2 - The 3′-end processing machinery for metazoan replication-dependent histone precursor messenger RNAs (pre-mRNAs) contains the U7 small nuclear ribonucleoprotein and shares the key cleavage module with the canonical cleavage and polyadenylation machinery. We reconstituted an active human histone pre-mRNA processing machinery using 13 recombinant proteins and two RNAs and determined its structure by cryo–electron microscopy. The overall structure is highly asymmetrical and resembles an amphora with one long handle. We captured the pre-mRNA in the active site of the endonuclease, the 73-kilodalton subunit of the cleavage and polyadenylation specificity factor, poised for cleavage. The endonuclease and the entire cleavage module undergo extensive rearrangements for activation, triggered through the recognition of the duplex between the authentic pre-mRNA and U7 small nuclear RNA (snRNA). Our study also has notable implications for understanding canonical and snRNA 3′-end processing.

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Structure of an active human histone pre-mRNA 3′-end processing machinery

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