publication . Article . Other literature type . 2019

Hatchet ribozyme structure and implications for cleavage mechanism.

Shuguang Yuan; Dinshaw J. Patel; Dinshaw J. Patel; Ronald Micura; Elisabeth Mairhofer; Aiming Ren; Juncheng Wang; Luqian Zheng; Kaiyi Huang; Christoph Falschlunger;
Open Access
  • Published: 01 May 2019 Journal: Proceedings of the National Academy of Sciences, volume 116, pages 10,783-10,791 (issn: 0027-8424, eissn: 1091-6490, Copyright policy)
  • Publisher: Proceedings of the National Academy of Sciences
Abstract
Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone with implications for viral genome replication, pre-mRNA processing, and alternative splicing. We report on the 2.1-Å crystal structure of the hatchet ribozyme product, which adopts a compact pseudosymmetric dimeric scaffold, with each monomer stabilized by long-range interactions involving highly conserved nucleotides brought into close proximity of the scissile phosphate. Strikingly, the catalytic pocket contains a cavity capable of accommodating both the modeled scissile phosphate and its flanking 5′ nucleoside. The resulting modeled precatalytic conformation in...
Subjects
free text keywords: Multidisciplinary, PNAS Plus, Biological Sciences, Biochemistry, hatchet, cleavage, catalysis, noncoding RNA, Phosphodiester bond, Nucleotide, chemistry.chemical_classification, chemistry, Nucleobase, Guanine, chemistry.chemical_compound, Cleavage (embryo), Viral genome replication, Stereochemistry, Ribozyme, biology.protein, biology, Nucleoside
Funded by
FWF| Chemical synthesis of modified twister ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 27947
  • Funding stream: Einzelprojekte
,
NIH| MOUSE GENETICS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Biochemical and structural characterization of RNA turnover processes and resolu
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U19CA179564-02
  • Funding stream: NATIONAL CANCER INSTITUTE
,
FWF| Understanding hatchet ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 31691
  • Funding stream: Einzelprojekte
35 references, page 1 of 3

1 Talini G, Branciamore S, Gallori E (2011) Ribozymes: Flexible molecular devices at work. Biochimie 93:1998–2005.21740954 [OpenAIRE] [PubMed]

2 Lilley DMJ (2017) How RNA acts as a nuclease: Some mechanistic comparisons in the nucleolyti c ribozymes. Biochem Soc Trans 45:683–691.28620029 [OpenAIRE] [PubMed]

3 Ren A, Micura R, Patel DJ (2017) Structure-based mechanistic insights into catalysis by small self-cleaving ribozymes. Curr Opin Chem Biol 41:71–83.29107885 [PubMed]

4 Jimenez RM, Polanco JA, Lupták A (2015) Chemistry and biology of self-cleaving ribozymes. Trends Biochem Sci 40:648–661.26481500 [OpenAIRE] [PubMed]

5 Weinberg Z, (2015) New classes of self-cleaving ribozymes revealed by comparative genomics analysis. Nat Chem Biol 11:606–610.26167874 [OpenAIRE] [PubMed]

6 Roth A, (2014) A widespread self-cleaving ribozyme class is revealed by bioinformatics. Nat Chem Biol 10:56–60.24240507 [OpenAIRE] [PubMed]

7 Martick M, Scott WG (2006) Tertiary contacts distant from the active site prime a ribozyme for catalysis. Cell 126:309–320.16859740 [OpenAIRE] [PubMed]

8 Mir A, Golden BL (2016) Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue. Biochemistry 55:633–636.26551631 [OpenAIRE] [PubMed]

9 Rupert PB, Ferré-D’AmaréAR (2001) Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis. Nature 410:780–786.11298439 [PubMed]

10 Rupert PB, Massey AP, Sigurdsson ST, Ferré-D’AmaréAR (2002) Transition state stabilization by a catalytic RNA. Science 298:1421–1424.12376595 [OpenAIRE] [PubMed]

11 Klein DJ, Ferré-D’AmaréAR (2006) Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 313:1752–1756.16990543 [PubMed]

12 Cochrane JC, Lipchock SV, Strobel SA (2007) Structural investigation of the GlmS ribozyme bound to its catalytic cofactor. Chem Biol 14:97–105.17196404 [OpenAIRE] [PubMed]

13 Ferré-D’AmaréAR, Zhou K, Doudna JA (1998) Crystal structure of a hepatitis delta virus ribozyme. Nature 395:567–574.9783582 [OpenAIRE] [PubMed]

14 Ke A, Zhou K, Ding F, Cate JH, Doudna JA (2004) A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature 429:201–205.15141216 [OpenAIRE] [PubMed]

15 Suslov NB, (2015) Crystal structure of the Varkud satellite ribozyme. Nat Chem Biol 11:840–846.26414446 [OpenAIRE] [PubMed]

35 references, page 1 of 3
Abstract
Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone with implications for viral genome replication, pre-mRNA processing, and alternative splicing. We report on the 2.1-Å crystal structure of the hatchet ribozyme product, which adopts a compact pseudosymmetric dimeric scaffold, with each monomer stabilized by long-range interactions involving highly conserved nucleotides brought into close proximity of the scissile phosphate. Strikingly, the catalytic pocket contains a cavity capable of accommodating both the modeled scissile phosphate and its flanking 5′ nucleoside. The resulting modeled precatalytic conformation in...
Subjects
free text keywords: Multidisciplinary, PNAS Plus, Biological Sciences, Biochemistry, hatchet, cleavage, catalysis, noncoding RNA, Phosphodiester bond, Nucleotide, chemistry.chemical_classification, chemistry, Nucleobase, Guanine, chemistry.chemical_compound, Cleavage (embryo), Viral genome replication, Stereochemistry, Ribozyme, biology.protein, biology, Nucleoside
Funded by
FWF| Chemical synthesis of modified twister ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 27947
  • Funding stream: Einzelprojekte
,
NIH| MOUSE GENETICS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Biochemical and structural characterization of RNA turnover processes and resolu
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U19CA179564-02
  • Funding stream: NATIONAL CANCER INSTITUTE
,
FWF| Understanding hatchet ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 31691
  • Funding stream: Einzelprojekte
35 references, page 1 of 3

1 Talini G, Branciamore S, Gallori E (2011) Ribozymes: Flexible molecular devices at work. Biochimie 93:1998–2005.21740954 [OpenAIRE] [PubMed]

2 Lilley DMJ (2017) How RNA acts as a nuclease: Some mechanistic comparisons in the nucleolyti c ribozymes. Biochem Soc Trans 45:683–691.28620029 [OpenAIRE] [PubMed]

3 Ren A, Micura R, Patel DJ (2017) Structure-based mechanistic insights into catalysis by small self-cleaving ribozymes. Curr Opin Chem Biol 41:71–83.29107885 [PubMed]

4 Jimenez RM, Polanco JA, Lupták A (2015) Chemistry and biology of self-cleaving ribozymes. Trends Biochem Sci 40:648–661.26481500 [OpenAIRE] [PubMed]

5 Weinberg Z, (2015) New classes of self-cleaving ribozymes revealed by comparative genomics analysis. Nat Chem Biol 11:606–610.26167874 [OpenAIRE] [PubMed]

6 Roth A, (2014) A widespread self-cleaving ribozyme class is revealed by bioinformatics. Nat Chem Biol 10:56–60.24240507 [OpenAIRE] [PubMed]

7 Martick M, Scott WG (2006) Tertiary contacts distant from the active site prime a ribozyme for catalysis. Cell 126:309–320.16859740 [OpenAIRE] [PubMed]

8 Mir A, Golden BL (2016) Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue. Biochemistry 55:633–636.26551631 [OpenAIRE] [PubMed]

9 Rupert PB, Ferré-D’AmaréAR (2001) Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis. Nature 410:780–786.11298439 [PubMed]

10 Rupert PB, Massey AP, Sigurdsson ST, Ferré-D’AmaréAR (2002) Transition state stabilization by a catalytic RNA. Science 298:1421–1424.12376595 [OpenAIRE] [PubMed]

11 Klein DJ, Ferré-D’AmaréAR (2006) Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 313:1752–1756.16990543 [PubMed]

12 Cochrane JC, Lipchock SV, Strobel SA (2007) Structural investigation of the GlmS ribozyme bound to its catalytic cofactor. Chem Biol 14:97–105.17196404 [OpenAIRE] [PubMed]

13 Ferré-D’AmaréAR, Zhou K, Doudna JA (1998) Crystal structure of a hepatitis delta virus ribozyme. Nature 395:567–574.9783582 [OpenAIRE] [PubMed]

14 Ke A, Zhou K, Ding F, Cate JH, Doudna JA (2004) A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature 429:201–205.15141216 [OpenAIRE] [PubMed]

15 Suslov NB, (2015) Crystal structure of the Varkud satellite ribozyme. Nat Chem Biol 11:840–846.26414446 [OpenAIRE] [PubMed]

35 references, page 1 of 3
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