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Trans-splicing enhances translational efficiency in C. elegans.

Yu-Fei Yang1,2,3, Xiaoqing Zhang1,2,3, Xuehua Ma2,4

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In Caenorhabditis elegans, trans-splicing with spliced leader 1 (SL1) enhances gene translational efficiency. This process likely improves the translation of essential genes by modifying the 5' untranslated region (5' UTR).

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Area of Science:

  • Molecular Biology
  • Genetics
  • Gene Regulation

Background:

  • Translational efficiency is crucial for gene expression but its regulatory factors are not fully understood.
  • In Caenorhabditis elegans, a significant portion of genes undergo trans-splicing with spliced leader 1 (SL1), replacing part of the 5' untranslated region (5' UTR).
  • The 5' UTR is known to play a critical role in regulating translational efficiency.

Purpose of the Study:

  • To investigate the hypothesis that SL1 trans-splicing regulates translational efficiency in Caenorhabditis elegans.
  • To elucidate the genomic mechanisms by which trans-splicing influences translational control.

Main Methods:

  • Genome-wide analysis of Ribo-seq data.
  • Polysome profiling experiments.
  • CRISPR-Cas9-based genetic manipulation of trans-splicing sites.

Main Results:

  • SL1 trans-spliced genes exhibit higher translational efficiencies compared to non-trans-spliced genes and orthologs in other nematodes.
  • Trans-splicing of an SL1 isoform increases translational efficiency compared to the non-trans-spliced isoform of the same gene.
  • Deletion of trans-splicing sites significantly reduces translational efficiency, particularly for essential genes.
  • SL1 trans-splicing enhances translational efficiency by shortening the 5' UTR, reducing upstream start codons (uAUGs), and weakening mRNA secondary structures.

Conclusions:

  • SL1 trans-splicing globally enhances translational efficiency in nematodes.
  • This mechanism plays a key role in boosting the translation of essential genes.
  • The findings provide insights into the genomic mechanisms governing translational regulation via trans-splicing.