scholarly journals All-Atom Simulations Decrypt the Molecular Terms of RNA Catalysis in the Exon-Ligation Step of the Spliceosome

ACS Catalysis ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 5328-5334 ◽  
Author(s):  
Jure Borišek ◽  
Alessandra Magistrato
Keyword(s):  
Rna Catalysis ◽  
Exon Ligation ◽  
Ligation Step

scholarly journals Branch site bulge conformations in domain 6 determine functional sugar puckers in group II intron splicing

2019 ◽  
Vol 47 (21) ◽  
pp. 11430-11440 ◽  
Author(s):  
Raphael Plangger ◽  
Michael Andreas Juen ◽  
Thomas Philipp Hoernes ◽  
Felix Nußbaumer ◽  
Johannes Kremser ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Conformational Dynamics ◽  
Group Ii Intron ◽  
Sugar Pucker ◽  
Branch Site ◽  
Exon Ligation ◽  
Catalytically Active ◽  
Group Ii ◽  
First Time ◽  
Ligation Step

Abstract Although group II intron ribozymes are intensively studied the question how structural dynamics affects splicing catalysis has remained elusive. We report for the first time that the group II intron domain 6 exists in a secondary structure equilibrium between a single- and a two-nucleotide bulge conformation, which is directly linked to a switch between sugar puckers of the branch site adenosine. Our study determined a functional sugar pucker equilibrium between the transesterification active C2′-endo conformation of the branch site adenosine in the 1nt bulge and an inactive C3′-endo state in the 2nt bulge fold, allowing the group II intron to switch its activity from the branching to the exon ligation step. Our detailed NMR spectroscopic investigation identified magnesium (II) ions and the branching reaction as regulators of the equilibrium populations. The tuneable secondary structure/sugar pucker equilibrium supports a conformational selection mechanism to up- and downregulate catalytically active and inactive states of the branch site adenosine to orchestrate the multi-step splicing process. The conformational dynamics of group II intron domain 6 is also proposed to be a key aspect for the directionality selection in reversible splicing.

scholarly journals Metal ion catalysis during the exon-ligation step of nuclear pre-mRNA splicing: Extending the parallels between the spliceosome and group II introns

RNA ◽  
2000 ◽  
Vol 6 (2) ◽  
pp. 199-205 ◽  
Author(s):  
PETER M. GORDON ◽  
ERIK J. SONTHEIMER ◽  
JOSEPH A. PICCIRILLI
Keyword(s):  
Metal Ion ◽  
Mrna Splicing ◽  
Group Ii Introns ◽  
Exon Ligation ◽  
Metal Ion Catalysis ◽  
Group Ii ◽  
Ligation Step

scholarly journals Ribozymes of the hepatitis delta virus: recent findings on their structure, mechanism of catalysis and possible applications.

2001 ◽  
Vol 48 (2) ◽  
pp. 409-418 ◽  
Author(s):  
J Ciesiolka ◽  
J Wrzesinski ◽  
M Legiewicz ◽  
B Smólska ◽  
M Dutkiewicz
Keyword(s):  
Hepatitis Delta Virus ◽  
Catalytic Properties ◽  
Rna Degradation ◽  
Base Catalysis ◽  
Rna Catalysis ◽  
X Ray ◽  
Rna Molecules ◽  
Mechanism Of Catalysis ◽  
Made In ◽  
Delta Virus

Although the delta ribozymes have been studied for more than ten years the most important information concerning their structure and mechanism of catalysis were only obtained very recently. The crystal structure of the genomic delta ribozyme turns out to be an excellent example of the extraordinary properties of RNA molecules to fold into uniquely compact structures. Details of the X-ray structure have greatly stimulated further studies on the folding of the ribozymes into functionally active molecules as well as on the mechanism of RNA catalysis. The ability of the delta ribozymes to carry out general acid-base catalysis by nucleotide side chains has been assumed in two proposed mechanisms of self-cleavage. Recently, considerable progress has been also made in characterizing the catalytic properties of trans-acting ribozyme variants that are potentially attractive tools in the strategy of directed RNA degradation.

A possible origin of RNA catalysis in multienzyme complexes

1989 ◽  
Vol 19 (1) ◽  
pp. 69-72 ◽  
Author(s):  
Matthew R. Edwards
Keyword(s):  
Rna Catalysis ◽  
Multienzyme Complexes

scholarly journals RNA Catalysis as a Probe for Chaperone Activity of DEAD-Box Helicases

2012 ◽  
pp. 111-130 ◽  
Author(s):  
Jeffrey P. Potratz ◽  
Rick Russell
Keyword(s):  
Chaperone Activity ◽  
Rna Catalysis ◽  
Dead Box

Exploitation of a thermosensitive splicing event to study pre-mRNA splicing in vivo

1988 ◽  
Vol 8 (4) ◽  
pp. 1558-1569
Author(s):  
P E Cizdziel ◽  
M de Mars ◽  
E C Murphy
Keyword(s):  
Splice Site ◽  
Rna Splicing ◽  
Mrna Splicing ◽  
Viral Rna ◽  
Temperature Sensitive ◽  
Exon Ligation ◽  
Branch Point Sequence ◽  
Infected Cells ◽  
Low Efficiency

The spliced form of MuSVts110 viral RNA is approximately 20-fold more abundant at growth temperatures of 33 degrees C or lower than at 37 to 41 degrees C. This difference is due to changes in the efficiency of MuSVts110 RNA splicing rather than selective thermolability of the spliced species at 37 to 41 degrees C or general thermosensitivity of RNA splicing in MuSVts110-infected cells. Moreover, RNA transcribed from MuSVts110 DNA introduced into a variety of cell lines is spliced in a temperature-sensitive fashion, suggesting that the structure of the viral RNA controls the efficiency of the event. We exploited this novel splicing event to study the cleavage and ligation events during splicing in vivo. No spliced viral mRNA or splicing intermediates were observed in MuSVts110-infected cells (6m2 cells) at 39 degrees C. However, after a short (about 30-min) lag following a shift to 33 degrees C, viral pre-mRNA cleaved at the 5' splice site began to accumulate. Ligated exons were not detected until about 60 min following the initial detection of cleavage at the 5' splice site, suggesting that these two splicing reactions did not occur concurrently. Splicing of viral RNA in the MuSVts110 revertant 54-5A4, which lacks the sequence -AG/TGT- at the usual 3' splice site, was studied. Cleavage at the 5' splice site in the revertant viral RNA proceeded in a temperature-sensitive fashion. No novel cryptic 3' splice sites were activated; however, splicing at an alternate upstream 3' splice site used at low efficiency in normal MuSVts110 RNA was increased to a level close to that of 5'-splice-site cleavage in the revertant viral RNA. Increased splicing at this site in 54-5A4 viral RNA is probably driven by the unavailability of the usual 3' splice site for exon ligation. The thermosensitivity of this alternate splice event suggests that the sequences governing the thermodependence of MuSVts110 RNA splicing do not involve any particular 3' splice site or branch point sequence, but rather lie near the 5' end of the intron.

RNA Catalysis and Transition State Stabilization

1996 ◽  
pp. 383-395 ◽  
Author(s):  
J. R. Prudent ◽  
P. G. Schultz
Keyword(s):  
Transition State ◽  
Rna Catalysis ◽  
Transition State Stabilization
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