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Related Concept Videos

RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
Transfer RNA Synthesis02:36

Transfer RNA Synthesis

One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
Pre-mRNA Processing: Modification of pre-mRNA Ends01:35

Pre-mRNA Processing: Modification of pre-mRNA Ends

In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...

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Related Experiment Video

Updated: Jun 12, 2026

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism
11:37

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Published on: July 28, 2017

5'-end uridine-derived base modification for siRNAs potency reinforcement.

Yuqi Yao1, Xinming Qi2,3, Ruimin Huang2

  • 1State Key Laboratory of Genetics and Development of Complex Phenotypes, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University, Shanghai, 200438, China.

Cell & Bioscience
|June 11, 2026
PubMed
Summary

Novel uridine-derived modifications significantly enhance small interfering RNA (siRNA) gene silencing potency. These modified siRNAs show improved binding and safety, offering new therapeutic potential.

Keywords:
5′-end nucleotide modificationArgonauteDrug safetyRNA silencingUridinesiRNA

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Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
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Nucleoside Triphosphates - From Synthesis to Biochemical Characterization

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Extremely Rapid and Specific Metabolic Labelling of RNA In Vivo with 4-Thiouracil (Ers4tU)
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Extremely Rapid and Specific Metabolic Labelling of RNA In Vivo with 4-Thiouracil (Ers4tU)

Published on: August 22, 2019

Related Experiment Videos

Last Updated: Jun 12, 2026

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism
11:37

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Published on: July 28, 2017

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
15:22

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization

Published on: April 3, 2014

Extremely Rapid and Specific Metabolic Labelling of RNA In Vivo with 4-Thiouracil (Ers4tU)
11:46

Extremely Rapid and Specific Metabolic Labelling of RNA In Vivo with 4-Thiouracil (Ers4tU)

Published on: August 22, 2019

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Small interfering RNAs (siRNAs) are crucial for gene silencing via mRNA cleavage.
  • Chemical modifications enhance siRNA stability and binding, with 5'-end modifications being key for potency.
  • The Argonaute-bound RISC complex mediates siRNA function through complementary base pairing.

Purpose of the Study:

  • To structurally analyze the 5'-end binding pocket of the RISC complex.
  • To design and screen novel uridine-derived modifications for enhanced siRNA potency.
  • To evaluate the in vitro and in vivo performance and safety of modified siRNAs.

Main Methods:

  • Structural analysis of the RISC complex's 5'-end binding pocket.
  • Design and synthesis of a library of uridine-derived siRNA modifications (001U-018U, vs30U).
  • In vitro RISC loading assays in HepG2 cells and in vivo RISC loading studies in mice.

Main Results:

  • Modified siRNAs demonstrated significantly improved gene silencing activity compared to controls.
  • In vitro and in vivo studies confirmed enhanced RISC loading and function.
  • Preliminary safety evaluations revealed no detectable cytotoxicity or genomic insertion risks.

Conclusions:

  • Novel uridine-derived modifications effectively enhance siRNA potency and gene silencing.
  • These modifications represent a promising advancement in siRNA drug design.
  • The findings expand the scope of chemical modifications for developing high-performance siRNA therapeutics.