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RNA, RNA interference, ribozyme switches, microRNA, structural studies, aptamers, and more ...

The importance of RNA interference was recognized by the Nobel Assembly, who awarded the 2006 Nobel Prize in Physiology or Medicine jointly to Andrew Z. Fire (Stanford School of Medicine, USA) and Craig C. Mello (University of Massachusetts, USA) for their discovery of RNA interference—gene silencing by double-stranded RNA.

Thomas Tuschl, winner of the Wiley Prize in Biomedical Sciences in 2003, discussed RNA Interference and Small Interfering RNAs in a Minireview in ChemBioChem, 2001, 2, 239.

Find all articles on RNA or just on RNA interference in Wiley Online Library...

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A Challenging Pie to Splice: Drugging the Spliceosome

A Challenging Pie to Splice: Drugging the Spliceosome

Over the last decade, considerable effort has been directed at developing drugs that target the spliceosome. The resulting synthetic and natural product splice modulators have opened new avenues for the interrogation of disease-associated splicing events. In this Minireview, an overview is provided of the recent advances in addressing the chemistry and chemical biology of the spliceosome and modulating its action with small molecules.

[Minireview]
Brian León, Manoj K. Kashyap, Warren C. Chan, Kelsey A. Krug, Januario E. Castro, James J. La Clair, Michael D. Burkart
Angew. Chem. Int. Ed., August 15, 2017, https://doi.org/10.1002/anie.201701065 Read article

Orotidine-Containing RNA: Implications for the Hierarchical Selection (Systems Chemistry Emergence) of RNA

Orotidine‐Containing RNA: Implications for the Hierarchical Selection (Systems Chemistry Emergence) of RNA

Presently absent: The presence of orotidine in prebiotic and de novo pathways coupled with its absence in RNA suggests a later emergence of RNA. Orotidine-containing RNA oligonucleotides have been investigated and it was found that they have severely compromised base-pairing properties (see scheme).

[Full Paper]
Eun-Kyong Kim, Vincent Martin, Ramanarayanan Krishnamurthy
Chem. Eur. J., August 11, 2017, https://doi.org/10.1002/chem.201702912 Read article

An L-RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA Biogenesis

An L‐RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA Biogenesis

Mirror images: By employing 5-aminoallyl-UTP during mirror image in vitro selection, a modified l-RNA aptamer was isolated with exceptional affinity towards oncogenic precursor microRNA-19a. These studies demonstrate that expanding the chemical functionality of l-aptamers enables development of robust RNA-binding reagents.

[Communication]
Adam M. Kabza, Jonathan T. Sczepanski
ChemBioChem, August 10, 2017, https://doi.org/10.1002/cbic.201700362 Read article

Optimized Solid-Phase-Assisted Synthesis of Oleic Acid Containing siRNA Nanocarriers

Optimized Solid‐Phase‐Assisted Synthesis of Oleic Acid Containing siRNA Nanocarriers

Better carriers for RNAi: Cationic lipo-oligomers containing cis-unsaturated fatty acids such as oleic acid are potent siRNA carriers which can be assembled by solid-phase-assisted synthesis. Trifluoroacetic acid (TFA)-mediated deprotection and cleavage of carriers from the resin may lead to side products initiated by the addition of TFA to the double bonds. The cleavage protocol was optimized to minimize TFA adducts, resulting (in comparison with the modified analogues) in beneficial siRNA delivery at low cytotoxicity.

[Full Paper]
Sören Reinhard, Wei Zhang, Ernst Wagner
ChemMedChem, August 07, 2017, https://doi.org/10.1002/cmdc.201700350 Read article

Analysis of Structure–Activity Relationships Based on the Hepatitis C Virus SLIIb Internal Ribosomal Entry Sequence RNA-Targeting GGHYRFK⋅Cu Complex

Analysis of Structure–Activity Relationships Based on the Hepatitis C Virus SLIIb Internal Ribosomal Entry Sequence RNA‐Targeting GGHYRFK⋅Cu Complex

Complexes to make SARs less complex: Based on a previously characterized HCV IRES stem-loop (SL) IIb RNA-targeting metallopeptide CuGGHYrFK, a series of substitution derivatives of the targeting domain (YrFK) have been characterized for binding and reactivity toward SLIIb RNA, and structurally modeled to yield insights into structure–function relationships that will guide future optimization efforts.

[Full Paper]
Martin James Ross, Insiya Fidai, James A. Cowan
ChemBioChem, August 07, 2017, https://doi.org/10.1002/cbic.201700228 Read article

Heterodimerization of Group I Ribozymes Enabling Exon Recombination through Pairs of Cooperative trans-Splicing Reactions

Heterodimerization of Group I Ribozymes Enabling Exon Recombination through Pairs of Cooperative trans‐Splicing Reactions

A cooperative trans-splicing system based on dimeric ribozymes derived from the Tetrahymena group I intron was developed through rational modular engineering. The resulting pairs of ribozymes exhibited catalytic activity depending on their selective dimerization and can conduct pairs of trans-splicing reactions.

[Full Paper]
Takahiro Tanaka, Yusuke Hirata, Yuto Tominaga, Hiroyuki Furuta, Shigeyoshi Matsumura, Yoshiya Ikawa
ChemBioChem, July 04, 2017, https://doi.org/10.1002/cbic.201700053 Read article

A Fluorescent RNA Forced-Intercalation Probe as a Pan-Selective Marker for Influenza A Virus Infection

A Fluorescent RNA Forced‐Intercalation Probe as a Pan‐Selective Marker for Influenza A Virus Infection

A good FIT: A pan-selective influenza A virus (IAV) probe, IAV QB-FIT, was designed to target the highly conserved IAV vRNA 5′-ends. This 2′-O-methylated RNA oligonucleotide and forced-intercalation dye-labeled probe is suitable to specifically detect IAV infections in fixed cells, independent of the cell line used, and can be employed to monitor different infection states.

[Communication]
Ivan Haralampiev, Matthias Schade, Jasmine Chamiolo, Fabian Jolmes, Simon Prisner, Peter T. Witkowski, Marie Behrent, Felix Hövelmann, Thorsten Wolff, Oliver Seitz, Andreas Herrmann
ChemBioChem, June 27, 2017, https://doi.org/10.1002/cbic.201700271 Read article

Conformational Dynamics of mRNA in Gene Expression as New Pharmaceutical Target

Conformational Dynamics of mRNA in Gene Expression as New Pharmaceutical Target

Recent functional studies demonstrate the importance of mRNA conformational dynamics in the regulation of gene expression and protein function. The structure, stability, and kinetic properties of nucleic acids are sensitive to the intracellular molecular environment, such as the concentrations of molecular crowding agents and molecules that interact with mRNA. Here, we review the roles of mRNA conformational dynamics in consecutive and concurrent processes involved in gene expression and discuss the possibility of using nucleic acid conformational dynamics as a basis of pharmaceutical drug development.

[Personal Account]
Tamaki Endoh, Naoki Sugimoto
Chem. Rec., May 17, 2017, https://doi.org/10.1002/tcr.201700016 Read article

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