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Related Concept Videos

MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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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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Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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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.
The chromatin structure, especially...
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Regulated mRNA Transport02:22

Regulated mRNA Transport

7.0K
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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pre-mRNA Processing02:01

pre-mRNA Processing

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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.
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 to it (7-Methyl...
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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
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MicroRNAs Enable mRNA Therapeutics to Selectively Program Cancer Cells to Self-Destruct.

Ruchi Jain1, Josh P Frederick2, Eric Y Huang3

  • 11 Department of Molecular Biology, Moderna Therapeutics , Cambridge, Massachusetts.

Nucleic Acid Therapeutics
|August 9, 2018
PubMed
Summary
This summary is machine-generated.

Therapeutic messenger RNAs (mRNAs) can be programmed to induce self-destruction in diseased cells. By incorporating microRNA target sites, toxic protein expression is limited to cancer cells, sparing healthy ones.

Keywords:
RNA modificationsmRNAmiRNAsuicide therapytherapeutic

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cancer Therapy

Background:

  • Therapeutic messenger RNAs (mRNAs) offer new avenues for protein-based biologics beyond traditional recombinant methods.
  • Potential applications include vaccines, immune-oncology, and protein replacement therapies.
  • A novel application is programming diseased cells to produce toxic proteins for self-destruction.

Purpose of the Study:

  • To develop a method for limiting toxic protein expression from therapeutic mRNAs to specific cell types.
  • To investigate the use of microRNA target sites for cell-specific control of apoptosis-inducing proteins.

Main Methods:

  • Designing therapeutic mRNAs encoding apoptotic proteins (Caspase, PUMA).
  • Incorporating microRNA target sites into these mRNAs.
  • Evaluating expression and apoptosis induction in hepatocellular carcinoma cells versus healthy hepatocytes.

Main Results:

  • MicroRNA target sites successfully prevented the expression of Caspase and PUMA in healthy hepatocytes.
  • Apoptosis was effectively triggered in hepatocellular carcinoma cells engineered to express these proteins.
  • This demonstrates cell-specific control over therapeutic mRNA-mediated cell death.

Conclusions:

  • Therapeutic mRNAs can be engineered for targeted cancer cell apoptosis.
  • MicroRNA targeting provides a mechanism for achieving cell-specific protein expression and therapeutic effect.
  • This approach holds promise for developing novel cancer therapies with reduced off-target toxicity.