Global Analysis of the Human RNA Degradome Reveals Widespread Decapped and Endonucleolytic Cleaved Transcripts

• Published in: International journal of molecular sciences 2020-09, Vol.21 (18), p.6452
• Main Authors: Won, Jung-Im, Shin, JaeMoon, Park, So Young, Yoon, JeeHee, Jeong, Dong-Hoon
• Format: Article
• Language: English
• Subjects: Base Sequence - genetics; By products; Cell lines; Databases, Genetic; decapping; Decay; Gene expression; Gene Expression Regulation - genetics; Genes; Genome - genetics; Genomes; HeLa Cells; High-Throughput Nucleotide Sequencing - methods; Histones - metabolism; Humans; Metabolism; mRNA decay; mRNA stability; Next-generation sequencing; parallel analysis of RNA ends; Polyadenylation; Post-transcription; Proteins; RNA Stability - physiology; RNA, Messenger - genetics; Sequence Analysis, RNA - methods; Whole Genome Sequencing - methods; XRN1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21186452

RNA decay is an important regulatory mechanism for gene expression at the posttranscriptional level. Although the main pathways and major enzymes that facilitate this process are well defined, global analysis of RNA turnover remains under-investigated. Recent advances in the application of next-generation sequencing technology enable its use in order to examine various RNA decay patterns at the genome-wide scale. In this study, we investigated human RNA decay patterns using parallel analysis of RNA end-sequencing (PARE-seq) data from -knockdown HeLa cell lines, followed by a comparison of steady state and degraded mRNA levels from RNA-seq and PARE-seq data, respectively. The results revealed 1103 and 1347 transcripts classified as stable and unstable candidates, respectively. Of the unstable candidates, we found that a subset of the transcripts was polyadenylated and rapidly degraded. Additionally, we identified 380 endonucleolytically cleaved candidates by analyzing the most abundant PARE sequence on a transcript. Of these, 41.4% of genes were classified as unstable genes, which implied that their endonucleolytic cleavage might affect their mRNA stability. Furthermore, we identified 1877 decapped candidates, including and having the most abundant PARE sequences at the 5'-end positions of the transcripts. These results provide a useful resource for further analysis of RNA decay patterns in human cells.