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Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site

RNA polymerase II (Pol II) incorporates complementary ribonucleotides into the growing RNA chain one at a time via the nucleotide addition cycle. The nucleotide addition cycle, however, is prone to misincorporation of noncomplementary nucleotides. Thus, to ensure transcriptional fidelity, Pol II bac...

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Autores principales: Unarta, Ilona Christy, Goonetilleke, Eshani C., Wang, Dong, Huang, Xuhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860460/
https://www.ncbi.nlm.nih.gov/pubmed/36581202
http://dx.doi.org/10.1016/j.jbc.2022.102844
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author Unarta, Ilona Christy
Goonetilleke, Eshani C.
Wang, Dong
Huang, Xuhui
author_facet Unarta, Ilona Christy
Goonetilleke, Eshani C.
Wang, Dong
Huang, Xuhui
author_sort Unarta, Ilona Christy
collection PubMed
description RNA polymerase II (Pol II) incorporates complementary ribonucleotides into the growing RNA chain one at a time via the nucleotide addition cycle. The nucleotide addition cycle, however, is prone to misincorporation of noncomplementary nucleotides. Thus, to ensure transcriptional fidelity, Pol II backtracks and then cleaves the misincorporated nucleotides. These two reverse reactions, nucleotide addition and cleavage, are catalyzed in the same active site of Pol II, which is different from DNA polymerases or other endonucleases. Recently, substantial progress has been made to understand how Pol II effectively performs its dual role in the same active site. Our review highlights these recent studies and provides an overall model of the catalytic mechanisms of Pol II. In particular, RNA extension follows the two-metal-ion mechanism, and several Pol II residues play important roles to facilitate the catalysis. In sharp contrast, the cleavage reaction is independent of any Pol II residues. Interestingly, Pol II relies on its residues to recognize the misincorporated nucleotides during the backtracking process, prior to cleavage. In this way, Pol II efficiently compartmentalizes its two distinct catalytic functions using the same active site. Lastly, we also discuss a new perspective on the potential third Mg(2+) in the nucleotide addition and intrinsic cleavage reactions.
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spelling pubmed-98604602023-01-26 Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site Unarta, Ilona Christy Goonetilleke, Eshani C. Wang, Dong Huang, Xuhui J Biol Chem JBC Reviews RNA polymerase II (Pol II) incorporates complementary ribonucleotides into the growing RNA chain one at a time via the nucleotide addition cycle. The nucleotide addition cycle, however, is prone to misincorporation of noncomplementary nucleotides. Thus, to ensure transcriptional fidelity, Pol II backtracks and then cleaves the misincorporated nucleotides. These two reverse reactions, nucleotide addition and cleavage, are catalyzed in the same active site of Pol II, which is different from DNA polymerases or other endonucleases. Recently, substantial progress has been made to understand how Pol II effectively performs its dual role in the same active site. Our review highlights these recent studies and provides an overall model of the catalytic mechanisms of Pol II. In particular, RNA extension follows the two-metal-ion mechanism, and several Pol II residues play important roles to facilitate the catalysis. In sharp contrast, the cleavage reaction is independent of any Pol II residues. Interestingly, Pol II relies on its residues to recognize the misincorporated nucleotides during the backtracking process, prior to cleavage. In this way, Pol II efficiently compartmentalizes its two distinct catalytic functions using the same active site. Lastly, we also discuss a new perspective on the potential third Mg(2+) in the nucleotide addition and intrinsic cleavage reactions. American Society for Biochemistry and Molecular Biology 2022-12-26 /pmc/articles/PMC9860460/ /pubmed/36581202 http://dx.doi.org/10.1016/j.jbc.2022.102844 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle JBC Reviews
Unarta, Ilona Christy
Goonetilleke, Eshani C.
Wang, Dong
Huang, Xuhui
Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site
title Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site
title_full Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site
title_fullStr Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site
title_full_unstemmed Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site
title_short Nucleotide addition and cleavage by RNA polymerase II: Coordination of two catalytic reactions using a single active site
title_sort nucleotide addition and cleavage by rna polymerase ii: coordination of two catalytic reactions using a single active site
topic JBC Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860460/
https://www.ncbi.nlm.nih.gov/pubmed/36581202
http://dx.doi.org/10.1016/j.jbc.2022.102844
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