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Nuclear Export of mRNA02:31

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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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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An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
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Adipocyte-selective mRNA lipid nanoparticles for cell programming with machine learning analysis.

Autumn Greco1, Leonardo Cheng1, Kailei Ding Goodier2

  • 1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|August 30, 2025
PubMed
Summary
This summary is machine-generated.

Researchers optimized lipid nanoparticles (LNPs) for targeted delivery of mRNA to white adipose tissue (WAT) cells. This breakthrough enhances adipocyte engineering for metabolic disease therapies.

Keywords:
Adipocyte engineeringAdipocyte-preferential transfectionFormulation screeningLipid nanoparticleMachine learning analysismRNA delivery

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Area of Science:

  • Biotechnology
  • Metabolic Engineering
  • Gene Therapy

Background:

  • Adipose tissue, particularly white adipose tissue (WAT), is vital for energy metabolism and endocrine signaling.
  • WAT is a key target for metabolic disease therapies due to its secretory functions and abundance.
  • Gene therapy offers potential for reprogramming adipocytes to improve energy metabolism and protein secretion.

Purpose of the Study:

  • To optimize messenger RNA (mRNA) lipid nanoparticles (LNPs) for preferential transfection of adipocytes.
  • To identify key features driving adipocyte selectivity in LNP delivery using machine learning.
  • To demonstrate effective and selective in vivo LNP-mediated mRNA delivery to adipocytes.

Main Methods:

  • Multi-step screening process to optimize mRNA LNP composition for adipocyte transfection.
  • Machine learning analysis to determine factors influencing adipocyte selectivity.
  • In vivo validation of LNP-mediated mRNA delivery in adipose tissue.

Main Results:

  • Successful optimization of mRNA LNPs for enhanced adipocyte-preferential transfection.
  • Identification of critical LNP features that promote adipocyte targeting.
  • Demonstration of potent and selective in vivo mRNA delivery to adipocytes.

Conclusions:

  • Optimizing LNP composition is crucial for efficient mRNA transfection in adipocytes.
  • This strategy provides a promising approach for adipocyte engineering.
  • The findings support therapeutic applications targeting metabolic diseases through adipocyte reprogramming.