UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene

Area of Science:

• Molecular biology
• Genetics
• Biochemistry

Background:

• DNA damage response is crucial for maintaining genomic integrity.
• Transcription regulation plays a key role in cellular responses to stress.
• Alternative splicing generates diverse RNA isoforms with distinct functions.

Purpose of the Study:

• To investigate the genome-wide transcriptional changes following UV-induced DNA damage.
• To elucidate the role of alternative last exons (ALEs) in the DNA damage response.
• To characterize the function of different ASCC3 transcript isoforms in transcription recovery.

Main Methods:

• Genome-wide analysis of transcription with high spatial and temporal resolution.
• UV irradiation of cells to induce DNA damage.
• Analysis of mRNA isoform shifts and their functional roles.

Main Results:

• UV irradiation causes transcriptional slowdown and restricts gene activity to promoter-proximal regions.
• A shift towards shorter mRNA isoforms, including those with alternative last exons (ALEs), is observed.
• A non-coding ASCC3 RNA isoform, generated via an ALE, is essential for transcription recovery after UV damage.
• The non-coding ASCC3 isoform antagonizes the function of the protein-coding ASCC3 isoform.

Conclusions:

• The ASCC3 gene produces antagonistic coding and non-coding transcript isoforms.
• These isoforms play critical, opposing roles in regulating transcription recovery post-UV DNA damage.
• Transcriptional regulation and alternative splicing are key components of the DNA damage response.