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Related Concept Videos

Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
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Regulated mRNA Transport02:22

Regulated mRNA Transport

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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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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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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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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.
Cis-acting Elements involved in mRNA stability
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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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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
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mRNA-Based Genetic Reprogramming.

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Molecular Therapy : the Journal of the American Society of Gene Therapy
|January 2, 2019
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Summary

Messenger RNA (mRNA) reprogramming offers a footprint-free method to convert skin cells into induced pluripotent stem cells (iPSCs). This technique is highly productive and suitable for clinical applications, overcoming previous genomic integration concerns.

Keywords:
cellular reprogrammingiPSCsinduced pluripotent stem cellsmRNA reprogrammingmessenger RNA reprogrammingmodified RNAsynthetic mRNA

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Area of Science:

  • Stem cell biology
  • Regenerative medicine
  • Genomic reprogramming

Background:

  • Induced pluripotent stem cells (iPSCs) hold promise for personalized regenerative treatments.
  • Early iPSC generation relied on integrating viral vectors, posing oncogenic risks.
  • Non-integrating reprogramming methods were developed to enhance safety.

Purpose of the Study:

  • To review the origins and advantages of mRNA-based reprogramming.
  • To discuss the benefits and limitations of mRNA reprogramming for clinical applications.
  • To outline current advancements and industrialization efforts for mass stem cell production.

Main Methods:

  • Utilizing messenger RNA (mRNA) to deliver reprogramming factors.
  • Employing non-integrating systems to avoid genomic alteration.
  • Focusing on methods suitable for large-scale clinical production.

Main Results:

  • mRNA reprogramming is a "footprint-free" method, minimizing genomic risks.
  • This technique demonstrates high productivity for generating iPSCs.
  • mRNA reprogramming is well-suited for the clinical-scale production of human stem cells.

Conclusions:

  • mRNA reprogramming represents a significant advancement over viral vector methods for iPSC generation.
  • The approach is highly efficient and safe, making it ideal for clinical translation.
  • Ongoing industrialization efforts aim to facilitate mass production of clinical-grade stem cells.