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UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene
- Source :
- Cell
- Publication Year :
- 2017
-
Abstract
- Summary The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ∼25 kb is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter ALE isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The non-coding ASCC3 isoform counteracts the function of the protein-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and non-coding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage.<br />Graphical Abstract<br />Highlights • UV elicits elongation slowdown and restricts transcription to the 5′ end of genes • UV induces a switch from long to short alternative last exon (ALE) transcript isoforms • ASCC3 short and long ALE isoforms have antagonistic functions in the UV response • The UV-induced ASCC3 short isoform functions as a long non-coding RNA<br />UV damage generates a functional non-coding RNA through alternative pre-mRNA processing of a damage response factor transcript, identifying a pathway for repurposing protein coding genes under selective conditions.
- Subjects :
- 0301 basic medicine
Gene isoform
RNA, Untranslated
Transcription Elongation, Genetic
Transcription, Genetic
Ultraviolet Rays
non-coding RNA
RNA polymerase II
DNA damage response
General Biochemistry, Genetics and Molecular Biology
Article
Cell Line
ASCC3
03 medical and health sciences
Exon
lncRNA
Transcription (biology)
Humans
RNA, Messenger
Gene
alternative last exon splicing
Transcription Initiation, Genetic
Messenger RNA
biology
Biochemistry, Genetics and Molecular Biology(all)
Alternative splicing
DNA Helicases
RNA
Exons
Molecular biology
Alternative Splicing
030104 developmental biology
biology.protein
transcript elongation
UV-irradiation
Subjects
Details
- Language :
- English
- ISSN :
- 10974172
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....02a756e4c3ce1ef7dac74ac07c56c6cf