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Related Concept Videos

mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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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.
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Related Experiment Video

Updated: Jun 21, 2025

Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery
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Branching in poly(amine-co-ester) polyplexes impacts mRNA transfection.

Kwangsoo Shin1, Hee-Won Suh2, Alexandra Suberi2

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA; Department of Polymer Science & Engineering and Program in Environmental and Polymer Engineering, Inha University, Incheon, 22212, Republic of Korea.

Biomaterials
|July 10, 2024
PubMed
Summary

Polymer branching significantly impacts mRNA delivery vehicles. Optimizing the degree of branching is crucial for enhancing polyplex stability and transfection efficiency in specific delivery routes.

Keywords:
Branched polymerNon-viral platformPolyplexmRNA deliverypoly(amino-co-ester)

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Area of Science:

  • Polymer Chemistry
  • Biomaterials Science
  • Gene Delivery

Background:

  • Polymer branching is a critical structural feature influencing material properties.
  • While known to affect mRNA delivery, the specific role of branching in cationic polymer vehicles is underexplored.
  • Previous research focused more on other polymer characteristics like composition and hydrophobicity.

Purpose of the Study:

  • To investigate the impact of polymer branching on the physicochemical properties of poly(amine-co-esters) (PACE).
  • To evaluate the efficiency of PACE polymers with varying degrees of branching in mRNA transfection both in vitro and in vivo.
  • To establish structure-property relationships for optimizing polymer-based nucleic acid delivery systems.

Main Methods:

  • Synthesis of poly(amine-co-esters) (PACE) with controlled degrees of branching (DB) from 0 to 0.66.
  • Systematic evaluation of physicochemical properties, including polyplex stability and pH buffering capacity.
  • In vitro and in vivo assessment of mRNA transfection efficiency using the synthesized PACE polymers.

Main Results:

  • Increasing the degree of branching enhanced the stability of polyplexes (mRNA-polymer complexes).
  • Branching was found to decrease the pH buffering capacity of the polymers.
  • Transfection efficiency varied with the degree of branching, indicating an optimal range for specific applications.

Conclusions:

  • Polymer branching is a key determinant of mRNA delivery vehicle performance.
  • The degree of branching requires optimization based on the specific delivery route and its associated physiological challenges.
  • This study provides critical insights into tailoring polymer architecture for effective nucleic acid delivery.