Molecular Biology

Silencing Mini-μ

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Science  06 May 2005:
Vol. 308, Issue 5723, pp. 759
DOI: 10.1126/science.308.5723.759e

Premature stop codons (PTCs) result in truncated proteins, species that would be extremely injurious. A post-transcriptional monitoring system—nonsense-mediated decay (NMD)—has evolved in eukaryotes to remove PTC-containing mRNAs before they can be translated. Immunoglobulin (Ig) genes are rearranged as part of normal lymphocyte development, and alleles containing PTCs are generated as nonfunctional byproducts of the process. Transcripts from these alleles are destroyed by NMD, but features of their extirpation suggest that something else is also suppressing these rogue mRNAs.

Bühler et al. have introduced PTCs into mouse Ig-μ minigenes and assayed their expression in tissue culture cells. They find that posttranscriptional NMD accounts for a 50% reduction in their expression. But they also find that 50% of the suppression occurs at the level of transcription and is mirrored by chromatin features associated with gene silencing: the loss of histone acetylation and an increase in methylation of histone H3 on the lysine-9 residue in the vicinity of the PTC-containing minigenes. Repression of putative small interfering RNAs (siRNAs) by overexpression of the siRNase 3'hExo abrogates the PTC-suppression effect, suggesting that RNA interference-related mechanisms may be involved. — GR

Mol. Cell 18, 307 (2005).

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