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Related Concept Videos

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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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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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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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Related Experiment Video

Updated: May 29, 2025

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast
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Structural basis of circularly permuted group II intron self-splicing.

Liu Wang1,2, Jiahao Xie1,3, Chong Zhang1

  • 1The State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital; The State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Nature Structural & Molecular Biology
|January 31, 2025
PubMed
Summary

Circularly permuted group II introns (CP introns) generate circular RNAs through a unique back-splicing mechanism. Cryo-EM structures reveal domain rearrangements and metal ion stabilization crucial for this process, advancing circRNA research.

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • RNA Biology

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their regulatory roles.
  • The biogenesis of circRNAs by circularly permuted group II introns (CP introns) is not well understood.
  • CP introns feature rearranged structural domains and tethered exons, leading to branched introns and circular exons.

Purpose of the Study:

  • To elucidate the structural and mechanistic basis of circRNA generation by CP introns.
  • To resolve the dynamic process of back-splicing in CP introns at high resolution.
  • To identify unique structural features and molecular interactions involved in CP intron splicing.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine high-resolution structures (2.5-2.9 Å).
  • Analysis of a natural CP intron in multiple functional states.
  • Comparative genomics to identify and analyze additional CP introns.

Main Results:

  • Detailed cryo-EM structures reveal domain 6 conformational changes facilitating 3'-exon recognition and circularization.
  • Unprecedented tertiary interactions were observed, compacting the catalytic triad and domain 6 for protein-independent splicing.
  • A specific metal ion (M35) was identified to stabilize the 5'-exon during the splicing reaction.
  • These unique features, distinct from canonical group II introns, are conserved in other CP introns.

Conclusions:

  • The study elucidates the dynamic mechanism of CP intron back-splicing, revealing key structural adaptations for circRNA formation.
  • Findings provide critical insights into the unique catalytic strategies of CP introns.
  • The results have significant implications for understanding circRNA biogenesis and developing novel circRNA-based therapeutics.