The PAICE suite reveals circadian posttranscriptional timing of noncoding RNAs and spliceosome components in Mus musculus macrophages.

Authors

• Sharleen M Buel
• Shayom Debopadhaya
• Hannah De Los Santos
• Kaelyn M Edwards
• Alexandra M David
• Uyen H Dao
• Kristin P Bennett
• Jennifer M Hurley

Publication/Presentation Date

8-25-2022

Abstract

Circadian rhythms broadly regulate physiological functions by tuning oscillations in the levels of mRNAs and proteins to the 24-h day/night cycle. Globally assessing which mRNAs and proteins are timed by the clock necessitates accurate recognition of oscillations in RNA and protein data, particularly in large omics data sets. Tools that employ fixed-amplitude models have previously been used to positive effect. However, the recognition of amplitude change in circadian oscillations required a new generation of analytical software to enhance the identification of these oscillations. To address this gap, we created the Pipeline for Amplitude Integration of Circadian Exploration suite. Here, we demonstrate the Pipeline for Amplitude Integration of Circadian Exploration suite's increased utility to detect circadian trends through the joint modeling of the Mus musculus macrophage transcriptome and proteome. Our enhanced detection confirmed extensive circadian posttranscriptional regulation in macrophages but highlighted that some of the reported discrepancy between mRNA and protein oscillations was due to noise in data. We further applied the Pipeline for Amplitude Integration of Circadian Exploration suite to investigate the circadian timing of noncoding RNAs, documenting extensive circadian timing of long noncoding RNAs and small nuclear RNAs, which control the recognition of mRNA in the spliceosome complex. By tracking oscillating spliceosome complex proteins using the PAICE suite, we noted that the clock broadly regulates the spliceosome, particularly the major spliceosome complex. As most of the above-noted rhythms had damped amplitude changes in their oscillations, this work highlights the importance of the PAICE suite in the thorough enumeration of oscillations in omics-scale datasets.

Volume

12

Issue

9

ISSN

2160-1836

Published In/Presented At

Buel, S. M., Debopadhaya, S., De Los Santos, H., Edwards, K. M., David, A. M., Dao, U. H., Bennett, K. P., & Hurley, J. M. (2022). The PAICE suite reveals circadian posttranscriptional timing of noncoding RNAs and spliceosome components in Mus musculus macrophages. G3 (Bethesda, Md.), 12(9), jkac176. https://doi.org/10.1093/g3journal/jkac176

Disciplines

Medicine and Health Sciences

PubMedID

35876788

Department(s)

Fellows and Residents

Document Type

Article