MicroRNAs as regulators of gene- and tissue-specific stop codon readthrough

Stop codon readthrough (SCR) refers to when the ribosome surpasses a stop codon, leading to the synthesis of elongated protein isoforms. Our recent study established the functional significance of tissue-specific SCR in multicellular organisms.

This research proposal aims to elucidate the mechanisms underlying gene- and tissue-specific SCR regulation.A recent breakthrough revealed that microRNAs (miRNAs) play a crucial role in regulating SCR in vivo, unveiling a novel function of miRNAs and an alternative gene regulation mechanism.

Building upon this discovery, our project seeks to unravel the regulatory pathways and biological implications of miRNA-mediated SCR within its physiological context.The primary aims are: (A) To gain a mechanistic understanding of gene- and tissue-specific SCR regulation, focusing on the influence of miRNAs; (B) To comprehensively map miRNA-driven regulation of SCR across the entire genome; (C) To employ an innovative approach using anti-sense oligonucleotides (ASOs) to mimic miRNA actions for targeted suppression of premature termination in a gene-specific manner.

By using the genetic tools of Drosophila for in vivo experiments and advanced molecular techniques in insect and human cell lines, we aim to attain a thorough comprehension of programmed SCR in vivo.

This intergative approach harbors significant potential for future treatment of cancer and genetic disorders stemming from nonsense mutations, with substantial medical and societal benefits.