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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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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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Replicative Cell Senescence02:15

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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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Regulation of Expression Occurs at Multiple Steps02:24

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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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Negative Regulator Molecules01:23

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Related Experiment Video

Updated: Jun 18, 2025

Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry
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RNA-based logic for selective protein expression in senescent cells.

Ward Jacobs1, Masoomeh Khalifeh1, Merijn Koot1

  • 1Department of Medical BioSciences, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands.

The International Journal of Biochemistry & Cell Biology
|August 1, 2024
PubMed
Summary

Researchers developed an mRNA logic circuit to detect and eliminate senescent cells. This system targets specific microRNA signatures, enabling precise cellular senescence detection and removal for potential therapeutic applications.

Keywords:
Cellular senescenceMiRNANanomedicineTherapeutic mRNA

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cell Biology

Background:

  • Cellular senescence, a state of irreversible growth arrest, contributes to age-related diseases.
  • Selective removal of senescent cells shows therapeutic potential in cancer and fibrosis.
  • Effective in vivo detection of senescent cells is crucial for understanding their role and treatment efficacy.

Purpose of the Study:

  • To develop a method for detecting and selectively removing senescent cells in vivo.
  • To engineer an mRNA logic circuit responsive to senescence-specific microRNA signatures.
  • To validate the utility of this system for therapeutic interventions.

Main Methods:

  • Induction and validation of radiation-induced senescence in primary human fibroblasts.
  • Identification of microRNAs (miRNAs) up- and downregulated during senescence using RT-qPCR.
  • Design of an mRNA logic circuit incorporating miRNA binding sites for senescence-specific protein expression.

Main Results:

  • Demonstrated senescence-specific expression of EGFP (Enhanced Green Fluorescent Protein) for senescent cell detection.
  • Achieved senescence-specific expression of constitutively active caspase-3 for selective cell removal.
  • Validated the functionality of the mRNA logic circuit in response to senescence-associated miRNA profiles.

Conclusions:

  • The developed mRNA logic circuit offers a novel strategy for targeting senescent cells.
  • This approach enables both the detection and selective elimination of senescent cells based on miRNA signatures.
  • Paves the way for mRNA-based therapeutic programs for senescent cell-related conditions.