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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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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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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
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Get Spliced: Uniting Alternative Splicing and Arthritis.

Maurice J H van Haaren1, Levina Bertina Steller1, Sebastiaan J Vastert1,2

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Alternative splicing, a key gene expression regulator, significantly impacts immune responses. Its dysregulation is linked to autoimmune diseases like arthritis, with potential therapeutic targets emerging from spliceform research.

Keywords:
alternative splicingarthritisimmunology

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Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Gene protein expression requires precise regulation during immune responses.
  • Alternative splicing (AS) is critical, affecting ~95% of protein-coding gene transcripts and enabling functional regulation via protein isoforms.
  • AS directly influences immune cell activation and has been linked to autoimmune diseases.

Purpose of the Study:

  • To review the role of alternative splicing in immune responses.
  • To explore how alternative splicing dysregulation contributes to arthritis pathogenesis.
  • To discuss therapeutic strategies targeting alternative splicing.

Main Methods:

  • Review of current literature on alternative splicing and immune responses.
  • Analysis of evidence linking alternative splicing to autoimmune diseases, particularly arthritis.
  • Examination of recent advances in long-read RNA sequencing for transcript isoform discovery.

Main Results:

  • Immune cell activation involves significant changes in isoform-level transcript expression.
  • Genome-wide association studies (GWASs) show enrichment of arthritis-associated SNPs in splice sites.
  • Thousands of novel transcript isoforms have been identified using advanced sequencing techniques.

Conclusions:

  • Alternative splicing plays a direct role in regulating immune responses.
  • Dysregulated alternative splicing is implicated in the pathogenesis of arthritis.
  • Modulating alternative splicing offers therapeutic potential, including biomarker development and targeted therapies.