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Related Concept Videos

RNA Splicing01:32

RNA Splicing

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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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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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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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Alternative RNA Splicing02:18

Alternative RNA Splicing

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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.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

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Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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  9. Predictive And Prognostic Markers
  11. Splicing Control By Phf5a Is Crucial For Melanoma Cell Survival

Splicing control by PHF5A is crucial for melanoma cell survival

Tina Meißgeier1, Melanie Kappelmann-Fenzl1,2, Sebastian Staebler1

  • 1Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Cell Proliferation
|August 30, 2024

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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Using the E1A Minigene Tool to Study mRNA Splicing Changes

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View abstract on PubMed

Summary
This summary is machine-generated.

PHD finger protein 5A (PHF5A) drives melanoma malignancy by causing splicing defects. PHF5A downregulation increases apoptosis, offering potential therapeutic targets for this aggressive skin cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alternative splicing abnormalities are key in cancer development.
  • Malignant melanoma, a deadly skin cancer, is associated with poor survival in patients with high PHF5A expression.

Purpose of the Study:

  • To investigate the role of splicing factor PHF5A in melanoma.
  • To explore PHF5A's impact on splicing, apoptosis, and its potential as a therapeutic target.

Main Methods:

  • siRNA-mediated downregulation of PHF5A in melanoma cell lines.
  • Analysis of splicing defects in tumor-relevant genes.
  • Investigation of apoptosis pathways, including Fas and unfolded protein response (UPR).

Main Results:

  • PHF5A downregulation caused significant splicing defects in melanoma cells.

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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Using the E1A Minigene Tool to Study mRNA Splicing Changes

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  • Loss of PHF5A induced apoptosis via Fas and UPR pathways.
  • These effects were specific to tumor cells, not observed in fibroblasts.

    • Conclusions:

    • PHF5A is a crucial driver of melanoma malignancy.
    • The identified splicing network regulated by PHF5A presents potential therapeutic targets for melanoma treatment.