Keeping cells fit

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Source: Science Magazine

Original: https://www.science.org/doi/abs/10.1126/science.aee7910?af=R...

Published: 2026-02-12T07:00:04Z

Cells transfer decay fragments of mutant messenger RNAs (mRNAs) from the cytoplasm to the nucleus to increase transcription of adapter genes.[1][4] Adapting genes are the mutated gene, its paralogs (genes created by duplication) and in some cases biologically related genes.[1] This mechanism is called transcriptional adaptation and serves as a double feedback and feedforward system to compensate for mutations in protein-coding genes.[1] The authors of El-Brolosy et al. identified the RNA binding protein ILF3 as a key link between cytoplasmic mRNA decay and nuclear transcription.[4] ILF3 is enriched in the RNA of adapter genes and its artificial binding promotes gene expression.[4] Using CRISPR and tiling oligonucleotide screens, they determined the precise mRNA decay fragments that trigger this response, with homology between trigger and target sequences playing a critical role.[4] Based on this understanding, they developed short nucleic acids that artificially activate the expression of target genes in cells.[1]