Abstract
The liver plays a pivotal role in metabolism and xenobiotic detoxification, processes that must be particularly efficient when animals are active and feed. A major question is how the liver adapts to these diurnal changes in physiology. Here, we show that, in mice, liver mass, hepatocyte size, and protein levels follow a daily rhythm, whose amplitude depends on both feeding-fasting and light-dark cycles. Correlative evidence suggests that the daily oscillation in global protein accumulation depends on a similar fluctuation in ribosome number. Whereas rRNA genes are transcribed at similar rates throughout the day, some newly synthesized rRNAs are polyadenylated and degraded in the nucleus in a robustly diurnal fashion with a phase opposite to that of ribosomal protein synthesis. Based on studies with cultured fibroblasts, we propose that rRNAs not packaged into complete ribosomal subunits are polyadenylated by the poly(A) polymerase PAPD5 and degraded by the nuclear exosome.
| Original language | English |
|---|---|
| Pages (from-to) | 651-663.e14 |
| Journal | Cell |
| Volume | 169 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 4 May 2017 |
Funding
We thank Andr? Liani and Yves-Alain Poget for designing and engineering the automated feeding machines; Pascal Gos for help in using them; Dr. Ingrid Grummt, DKFZ, Heidelberg, for providing anti-RNA polymerase I antibodies; and Nicolas Roggli for the artwork. Dr. Charna Dibner, the current employer of F.S., Geneva Medical School, has generously allocated her time for conducting the revisions. We thank Jessica Sordet-Dessimoz, Histology Core Facility, EPFL, for her assistance in the immunohistochemistry experiments. Work in the laboratory of U.S. was supported by the Swiss National Science Foundation (SNF 31-113565 and SNF 31-128656/1), the European Research Council (ERC-2009-AdG-TIMESIGNAL-250117), the State of Geneva, and the Louis Jeantet Foundation of Medicine. F.S. was funded in part by a long-term EMBO fellowship (ALTF 1464-2012). Work in the laboratory of C.B.G. was funded by the NIH (R01GM111387, R01GM112991, and R01AG045795). D.G. acknowledges funding by SNF professorship grant 157528 and the NCCR RNA & Disease. F.G. acknowledges funding by the European Research Council (through individual starting grants ERC-2010-StG-CIRCATRANS-260988) and the Leenaards Foundation (to F.G. and D.G.). F.G. and D.M. are Nestl? Institute of Health Sciences SA employees.
| Funders | Funder number |
|---|---|
| Louis Jeantet Foundation of Medicine | |
| NCCR RNA & Disease | ERC-2010-StG-CIRCATRANS-260988 |
| Nestlé Institute of Health Sciences | |
| State of Geneva | |
| National Institutes of Health | R01GM112991, 157528, R01AG045795 |
| National Institute of General Medical Sciences | R01GM111387 |
| European Molecular Biology Organization | ALTF 1464-2012 |
| Deutsches Krebsforschungszentrum | |
| European Research Council | ERC-2009-AdG-TIMESIGNAL-250117 |
| Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung | 31-128656/1, 31-113565 |
| Fondation Leenaards |
Keywords
- cell size
- circadian
- diurnal
- feeding-fasting rhythms
- liver
- mouse
- ribosomal protein synthesis
- rRNA degradation
- rRNA polyadenylation
- TRAMP complex