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

dc.contributor.authorUnruh, Benjamin A.en
dc.contributor.authorWeidemann, Douglas E.en
dc.contributor.authorMiao, Linen
dc.contributor.authorKojima, Shihokoen
dc.date.accessioned2024-02-29T12:50:49Zen
dc.date.available2024-02-29T12:50:49Zen
dc.date.issued2024en
dc.description.abstractCircadian 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.en
dc.description.sponsorshipThis work was supported by NIH F31 AG071393 (to B.A.U) and R01 GM126223 (to S.K.).en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1073/pnas.2314690121en
dc.identifier.issue7en
dc.identifier.urihttps://hdl.handle.net/10919/118207en
dc.identifier.volume121en
dc.language.isoenen
dc.publisherNational Academy of Sciencesen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectcircadian rhythmsen
dc.subject4-thiouridineen
dc.subjectrhythmic gene expressionen
dc.subjectRNA dynamicsen
dc.subjectmetabolic labelingen
dc.titleCoordination of rhythmic RNA synthesis and degradation orchestrates 24-and 12-h RNA expression patterns in mouse fibroblastsen
dc.title.serialPNASen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
unruh-et-al-2024.pdf
Size:
2.28 MB
Format:
Adobe Portable Document Format
Description:
Published version
License bundle
Now showing 1 - 1 of 1
Name:
license.txt
Size:
1.5 KB
Format:
Item-specific license agreed upon to submission
Description: