非表示:
キーワード:
CRISPR/Cas9 , Drosophila melanogaster, eRF1H
要旨:
Translational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon,
resulting in two protein isoforms synthesized from
the same mRNA. TR has been identified in several
eukaryotic organisms; however, its biological significance and mechanism remain unclear. Here, we
quantify TR of several candidate genes in
Drosophila
melanogaster and characterize the regulation of TR
in the large Maf transcription factor Traffic jam
(Tj). Using CRISPR/Cas9-generated mutant flies, we
show that the TR-generated Tj isoform is expressed
in a subset of neural cells of the central nervous
system and is excluded from the somatic cells of
gonads. Control of TR in Tj is critical for preservation of neuronal integrity and maintenance of reproductive health. The tissue-specific distribution of a
release factor splice variant, eRF1H, plays a critical
role in modulating differential TR of leaky stop codon
contexts. Finetuning of gene regulatory functions
of transcription factors by TR provides a potential
mechanism for cell-specific regulation of gene ex-pression.
