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Alternative RNA Splicing02:18

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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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The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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Reciprocal regulation between alternative splicing and the DNA damage response.

Adrian E Cambindo Botto1, Juan C Muñoz1, Luciana E Giono1

  • 1Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiologia, Biologia Molecular y Celular, Instituto de Fisiologia, Biologia Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.

Genetics and Molecular Biology
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Summary

Cells adapt to DNA damage by altering gene expression through alternative splicing. DNA damage response kinases regulate this process, which in turn influences the cell

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Alternative splicing generates diverse RNA isoforms from a single gene, modulating cellular responses.
  • Approximately 95% of the human coding genome is regulated by alternative splicing.
  • The DNA damage response (DDR) pathway is known to be influenced by alternative splicing.

Purpose of the Study:

  • To investigate the interplay between DNA damage response kinases and alternative splicing.
  • To understand how alternative splicing modulates the cellular response to genotoxic insults.

Main Methods:

  • The study likely involves analyzing gene expression and splicing patterns in response to genotoxic agents.
  • Investigating the role of specific DNA damage response kinases (ATM, ATR, DNA-PK) in regulating alternative splicing.

Main Results:

  • Genotoxic insults trigger DNA damage response kinases (ATM, ATR, DNA-PK) to orchestrate gene expression.
  • These kinases modulate alternative splicing patterns in response to DNA damage.
  • Alternative splicing, in turn, influences the cellular response to DNA damaging agents.

Conclusions:

  • Alternative splicing is a critical component of the DNA damage response.
  • A reciprocal relationship exists between DNA damage response pathways and alternative splicing.
  • Modulation of alternative splicing is essential for cellular adaptation to genotoxic stress.