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Related Concept Videos

RNA Splicing01:32

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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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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.
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Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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An Intricate Connection between Alternative Splicing and Phenotypic Plasticity in Development and Cancer.

Giuseppe Biamonti1, Lucia Infantino1, Daniela Gaglio2,3

  • 1Institute of Molecular Genetics (IGM); National Research Council (CNR), 27100 Pavia, Italy.

Cells
|December 28, 2019
PubMed
Summary

Cancer cells adapt to harsh conditions through cellular plasticity, often involving stem pathways and alternative splicing (AS). Understanding AS

Keywords:
EMTalternative splicingcancer metabolismcancer stem cellscellular plasticityneo-angiogenesistumor heterogeneity

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tumor progression involves cancer cell adaptation to microenvironmental challenges like hypoxia and drug treatment.
  • Cellular plasticity enhances cancer cell survival, drug resistance, and metastasis.
  • Re-activation of stem pathways drives cellular plasticity, promoting stem-like properties and tumor heterogeneity.

Purpose of the Study:

  • To investigate the role of alternative splicing (AS) in cancer cell plasticity and tumor heterogeneity.
  • To elucidate the molecular mechanisms linking AS to the maintenance of a stem-like phenotype.
  • To explore the potential of AS as a diagnostic and therapeutic target in cancer.

Main Methods:

  • Review of high-throughput sequencing technologies.
  • Analysis of alternative splicing (AS) in cancer cell plasticity.
  • Exploration of the relationship between AS and stem-like phenotypes.

Main Results:

  • Alternative splicing (AS) is a key mechanism increasing transcriptome and proteome diversity.
  • Defective AS is linked to various human diseases.
  • The precise role of AS in cancer cell plasticity and tumor heterogeneity requires further investigation.

Conclusions:

  • Alternative splicing (AS) plays a significant role in cancer cell plasticity and tumor heterogeneity.
  • Understanding the AS-stem-like phenotype connection can reveal cancer mechanisms.
  • Targeting AS may offer new avenues for cancer diagnosis and treatment.