Editors' ChoiceImmunology

UV radiation induces a gene’s dual functionality

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Sci. Signal.  07 Mar 2017:
Vol. 10, Issue 469, eaan0919
DOI: 10.1126/scisignal.aan0919

A protein and noncoding RNA encoded by the same gene have opposing roles in the response to UV radiation–induced damage.

The same nucleotide sequence can sometimes produce both a regulatory RNA and a functional protein. The protein and RNA produced from the same sequence often have related roles. Williamson et al. found that ASCC3, a transcription factor that regulates the responses of many genes to ultraviolet (UV) radiation, is regulated by an isoform of the ASCC3 transcript that is produced by UV damage and that functions as a long noncoding RNA. UV treatment of human fibroblast cultures caused genome-wide stalling of transcriptional elongation, resulting in a high frequency of shorter RNA isoforms, including some with alternative last exons. One of the UV-induced short alternative isoforms originated from the ASCC3 gene. The full-length ASCC3 transcript produced a protein that acted as a global suppressor of transcription initiation in the late stages of cellular responses to UV exposure. In contrast, the short ASCC3 isoform was required for recovery of transcription. Ectopic expression of the protein-coding portion of the short isoform did not recapitulate its function, whereas a mutant of the short isoform with a premature stop codon that prevented the production of any protein was functional, indicating that the short isoform’s regulatory function was as a noncoding RNA. This study illustrates how dual-function genes can integrate responses to an environmental cue by producing both a protein and regulatory long noncoding RNA. Because Williamson et al. found that the protein and the noncoding RNA produced by the same gene had opposing functions, these results indicate that caution is warranted when using transcription as a proxy for function. Szempruch and Guttman speculate about the potential advantages of encoding proteins and noncoding RNAs from within the same genes.

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