Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver

PLoS Genet. 2022 Aug 3;18(8):e1009903. doi: 10.1371/journal.pgen.1009903. eCollection 2022 Aug.

Abstract

In eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of RNA accumulation and affecting the distribution of transcripts in different subcellular compartments. Our study analysed the nuclear and cytoplasmic, poly(A) and total transcriptomes of mouse livers collected over the course of a day. These data provide a genome-wide temporal inventory of enrichment in subcellular RNA, and revealed specific signatures of splicing, nuclear export and cytoplasmic mRNA stability related to transcript and gene lengths. Combined with a mathematical model describing rhythmic RNA profiles, we could test the rhythmicity of export rates and cytoplasmic degradation rates of approximately 1400 genes. With nuclear export times usually much shorter than cytoplasmic half-lives, we found that nuclear export contributes to the modulation and generation of rhythmic profiles of 10% of the cycling nuclear mRNAs. This study contributes to a better understanding of the dynamic regulation of the transcriptome during the day-night cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus* / genetics
  • Cell Nucleus* / metabolism
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Liver / metabolism
  • Mice
  • RNA / metabolism
  • Transcriptome* / genetics

Substances

  • RNA

Grants and funding

This work was supported by the Swiss National Science Foundation (SNSF) project grants 310030_173079 and 310030B_201267 (to F.N.), and the EPFL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.