Mechanism of pre-mRNA trans-splicing

Genes contain the instructions for producing specific proteins. Life relies on the combined actions of thousands of genes, each producing its own protein. However, within our DNA, these valuable instructions are interrupted by long, non-coding sequences that obscure the genetic codelike a sentence cluttered with random letters. To make the genetic code readable by the cell, the gene is first copied into a different class of biomolecule known as mRNA, which functions as a messenger. This mRNA copy is then edited to remove the non-coding sequences, creating a functional blueprint. This crucial editing process is called splicing. Typically, splicing occurs within a single RNA molecule (cis-splicing). However, in many organisms, such as certain parasites and plants, segments of RNA from different molecules are joined together to form a functional `blueprint`a process called trans-splicing. While trans- splicing is common in many organisms, much remains unknown about how it works at the molecular level. My research focuses on studying trans-splicing in C. elegans as a model organism. I will use advanced imaging techniques, such as cryo-electron microscopy, to visualize the molecular machinery responsible for this process, known as the trans-spliceosome. By uncovering how the trans-spliceosome identifies and links RNA segments, we aim to gain fundamental insights into this essential process. Understanding trans-splicing is not only critical for advancing basic science but could also have far-reaching implications. It may enhance our understanding of how RNA processing evolved, provide new insights into gene regulation in parasites, and potentially lead to innovative strategies for bio-engineering and combating parasitic diseases.

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