Cellular fractionation reveals transcriptome responses of human fibroblasts (MRC5_VA cells and CS1AN cells) to UV-C irradiation

ABSTRACT: Cells activate a multifaceted DNA damage response to remove transcription-blocking DNA lesions, The genome-wide reduction of RNA synthesis and the paradoxical continuous loading of RNAP II at initiation sites is still poorly understood. Uncovering how dramatic changes to the transcriptional program contribute to TC-NER (transcription-coupled nucleotide excision repair) comprises one of the most fascinating frontiers in DNA repair research. Here we examined UV-induced gene regulation in human fibroblasts by performing RNA-seq with fractionated chromatin-associated and cytoplasmic transcripts. This approach allowed us to separate the synthesis of nascent transcripts from the accumulation of mature RNAs. In addition to documenting the subcellular locations of coding transcripts, our results also provide a high-resolution view of the transcription activities of noncoding RNAs in response to cellular stress. At the same time, the data showed that vast majority of chromatin-enriched DNA damage response transcripts are cis-acting. Distinct from coding genes that transcripts with shorter length are prefered to be recovered first, repression of lncRNA transcription after UV exposure is inactivated first on noncoding transcripts with longer length. This work provides an updated framework for cellular RNA organization in response to stress and may prove useful in understanding how cells respond to transcription-blocking DNA damage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184408 | GEO | 2021/09/22

REPOSITORIES: GEO