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. 2014 Nov 15;28(22):2447-9.
doi: 10.1101/gad.254193.114.

Nonsense-mediated RNA Decay: At the 'Cutting Edge' of Regulated snoRNA Production

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Free PMC article

Nonsense-mediated RNA Decay: At the 'Cutting Edge' of Regulated snoRNA Production

Jeremy E Wilusz et al. Genes Dev. .
Free PMC article

Abstract

Production of multiple functional RNAs from a single primary transcript is an extremely efficient use of genetic information, although it complicates the ability of the cell to independently regulate the production of each RNA. For the case of small nucleolar RNAs (snoRNAs) encoded within introns of mRNA genes, Lykke-Andersen and colleagues (pp. 2498-2517) demonstrated that alternative splicing and the SMG6 endonuclease of the nonsense-mediated RNA decay pathway are key regulators that control which RNAs accumulate.

Keywords: RNA decapping; endonucleolytic RNA cleavage; intron-encoded snoRNA; nonsense-mediated decay; regulation of snoRNA expression; snoRNA host genes.

Figures

Figure 1.
Figure 1.
Alternative splicing coupled to NMD regulates the output of snoRNA host genes. (Middle) A model gene that hosts two snoRNAs is subjected to alternative splicing. (Top) When the transcript is spliced such that all introns are removed, a stable protein-coding mRNA and two snoRNA-containing intron lariats are produced. Following lariat debranching and trimming by exonucleases, the mature snoRNAs are released. (Bottom) If the pre-mRNA is instead spliced such that intron 2 is retained in the mature mRNA, only the snoRNA derived from the first intron is produced. Intron retention additionally causes a PTC to be present in the mRNA, which triggers NMD and endonucleolytic cleavage of the mRNA by SMG6. The two halves of the cleaved mRNA are subsequently rapidly degraded by exonucleases, such as XRN1 and the exosome. By finely regulating these alternative splicing and NMD events, the cell is able to ensure differential expression of the individual snoRNAs, spliced mRNAs, and proteins from this multifunctional gene.

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