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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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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.
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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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Non-LTR Retrotransposons03:18

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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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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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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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PELP1 oncogenic functions involve alternative splicing via PRMT6.

Monica Mann1, Yi Zou2, Yidong Chen2

  • 1The Department of Cellular and Structural Biology, San Antonio, TX 78229, USA; The Department of Obstetrics and Gynecology, San Antonio, TX 78229, USA.

Molecular Oncology
|January 23, 2014
PubMed
Summary

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) drives breast cancer by regulating alternative splicing. Targeting the PELP1-PRMT6 axis offers a new therapeutic strategy for breast cancer patients.

Keywords:
Alternative splicingBreast cancerEpigeneticsPELP1PRMT6

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Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a proto-oncogene implicated in breast cancer progression, metastasis, and therapy resistance.
  • PELP1 acts as a coactivator for the estrogen receptor and is linked to poorer patient survival.
  • The full spectrum of PELP1 target genes and its precise oncogenic mechanisms remain incompletely understood.

Purpose of the Study:

  • To comprehensively identify PELP1-regulated genes across the genome.
  • To elucidate the molecular mechanisms underlying PELP1-mediated oncogenesis, including its role in alternative splicing.
  • To investigate the potential of the PELP1-PRMT6 interaction as a therapeutic target in breast cancer.

Main Methods:

  • Whole genome RNA-sequencing (RNA-seq) to profile the PELP1 transcriptome.
  • Bioinformatic pathway analysis of identified PELP1-regulated genes.
  • Mechanistic studies involving RNA binding assays, co-localization studies with SC35, and interaction studies with PRMT6.

Main Results:

  • Identified 318 PELP1-regulated genes, revealing PELP1's modulation of cancer, estrogen signaling, and breast cancer progression pathways.
  • Discovered that PELP1 regulates alternative splicing, leading to unique spliced isoforms.
  • Demonstrated PELP1's interaction with PRMT6, influencing its function and co-recruitment to estrogen receptor target genes, impacting histone modifications and alternative splicing of cancer-related genes.

Conclusions:

  • PELP1 promotes oncogenesis through alternative splicing, activating unique pathways that drive tumor progression.
  • The PELP1-PRMT6 axis plays a critical role in regulating alternative splicing in breast cancer.
  • Targeting the PELP1-PRMT6 interaction presents a promising therapeutic strategy for breast cancer treatment.