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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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A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
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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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Chemically Modified mocRNAs for Highly Efficient Protein Expression in Mammalian Cells.

Abhishek Aditham1,2, Hailing Shi1,3, Jianting Guo1,3

  • 1Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.

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Messenger-oligonucleotide conjugated RNAs (mocRNAs) enhance protein production by protecting mRNA poly(A) tails. This novel RNA platform boosts protein expression efficiency and stability for research and therapeutics.

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Area of Science:

  • Molecular Biology
  • Biotechnology
  • Drug Delivery

Background:

  • Messenger RNA (mRNA) is a versatile platform for rapid in vivo protein production.
  • Current mRNA technology faces limitations in translational capacity and RNA stability.
  • Chemical modifications are key to improving mRNA therapeutic potential.

Purpose of the Study:

  • To introduce messenger-oligonucleotide conjugated RNAs (mocRNAs) as a novel RNA platform.
  • To enhance mRNA stability and translational efficiency through chemical modification.
  • To explore mocRNAs for improved protein expression in research and therapeutic applications.

Main Methods:

  • Chemically synthesized oligonucleotides were ligated to the 3' terminus of mRNA.
  • mocRNA constructs were designed to protect poly(A) tails from degradation.
  • Protein production was quantified in human HeLa cells and primary rat cortical neuronal cultures.

Main Results:

  • mocRNAs with deadenylase-resistant oligonucleotides significantly augmented protein production.
  • Protein expression increased 2-4 fold in HeLa cells and 10-fold in neuronal cultures.
  • The mocRNA design demonstrated robust and modular encoding of chemical modifications.

Conclusions:

  • mocRNAs offer a strategy to overcome limitations in mRNA translational capacity and stability.
  • This approach enables highly efficient and stable protein expression.
  • mocRNA technology expands the potential of RNA-based vectors for diverse applications.