Coordination of rhythmic RNA synthesis and degradation orchestrates 24- and 12-h RNA expression patterns in mouse fibroblasts.

Autor: Unruh BA; Department of Biological Sciences, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061., Weidemann DE; Department of Biological Sciences, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061., Miao L; Department of Biological Sciences, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061., Kojima S; Department of Biological Sciences, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Feb 13; Vol. 121 (7), pp. e2314690121. Date of Electronic Publication: 2024 Feb 05.
DOI: 10.1073/pnas.2314690121
Abstrakt: Circadian RNA expression is essential to ultimately regulate a plethora of downstream rhythmic biochemical, physiological, and behavioral processes. Both transcriptional and posttranscriptional mechanisms are considered important to drive rhythmic RNA expression; however, the extent to which each regulatory process contributes to the rhythmic RNA expression remains controversial. To systematically address this, we monitored RNA dynamics using metabolic RNA labeling technology during a circadian cycle in mouse fibroblasts. We find that rhythmic RNA synthesis is the primary contributor of 24-h RNA rhythms, while rhythmic degradation is more important for 12-h RNA rhythms. These rhythms were predominantly regulated by Bmal1 and/or the core clock mechanism, and the interplay between rhythmic synthesis and degradation has a significant impact in shaping rhythmic RNA expression patterns. Interestingly, core clock RNAs are regulated by multiple rhythmic processes and have the highest amplitude of synthesis and degradation, presumably critical to sustain robust rhythmicity of cell-autonomous circadian rhythms. Our study yields invaluable insights into the temporal dynamics of both 24- and 12-h RNA rhythms in mouse fibroblasts.
Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze: MEDLINE