TY - JOUR
T1 - Achilles-Mediated and Sex-Specific Regulation of Circadian mRNA Rhythms in Drosophila
AU - Li, Jiajia
AU - Yu, Renee Yin
AU - Emran, Farida
AU - Chen, Brian E.
AU - Hughes, Michael E.
N1 - Funding Information:
We thank Jeanne Geskes, Robert Lyons, and the University of Michigan DNA sequencing core facility for assistance with next-generation sequencing. We thank members of the Hughes and Chen laboratories for helpful discussion and technical support throughout this project as well as revisions on the manuscript. We thank especially Erin Terry, Ayesha Baig, Jason Bedwinek, Christy Hoffman and Kylie Mink for technical support during the course of this work. We thank Dr. Nicholas Lahens (University of Pennsylvania) and Dr. Malcolm Tobias (Washington University in St. Louis) for bioinformatics technical support. We thank the Holtzman, Nerbonne, Skeath and Taghert labs (Washington University in St. Louis) for help with equipment and reagents. Jiajia Li was supported by dissertation fellowship (University of Missouri-St. Louis). Work in the Hughes Lab is supported by an award from NIAMS (1R21AR069266).
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/4/1
Y1 - 2019/4/1
N2 - The circadian clock is an evolutionarily conserved mechanism that generates the rhythmic expression of downstream genes. The core circadian clock drives the expression of clock-controlled genes, which in turn play critical roles in carrying out many rhythmic physiological processes. Nevertheless, the molecular mechanisms by which clock output genes orchestrate rhythmic signals from the brain to peripheral tissues are largely unknown. Here we explored the role of one rhythmic gene, Achilles, in regulating the rhythmic transcriptome in the fly head. Achilles is a clock-controlled gene in Drosophila that encodes a putative RNA-binding protein. Achilles expression is found in neurons throughout the fly brain using fluorescence in situ hybridization (FISH), and legacy data suggest it is not expressed in core clock neurons. Together, these observations argue against a role for Achilles in regulating the core clock. To assess its impact on circadian mRNA rhythms, we performed RNA sequencing (RNAseq) to compare the rhythmic transcriptomes of control flies and those with diminished Achilles expression in all neurons. Consistent with previous studies, we observe dramatic upregulation of immune response genes upon knock-down of Achilles. Furthermore, many circadian mRNAs lose their rhythmicity in Achilles knock-down flies, suggesting that a subset of the rhythmic transcriptome is regulated either directly or indirectly by Achilles. These Achilles-mediated rhythms are observed in genes involved in immune function and in neuronal signaling, including Prosap, Nemy and Jhl-21. A comparison of RNAseq data from control flies reveals that only 42.7% of clock-controlled genes in the fly brain are rhythmic in both males and females. As mRNA rhythms of core clock genes are largely invariant between the sexes, this observation suggests that sex-specific mechanisms are an important, and heretofore under-appreciated, regulator of the rhythmic transcriptome.
AB - The circadian clock is an evolutionarily conserved mechanism that generates the rhythmic expression of downstream genes. The core circadian clock drives the expression of clock-controlled genes, which in turn play critical roles in carrying out many rhythmic physiological processes. Nevertheless, the molecular mechanisms by which clock output genes orchestrate rhythmic signals from the brain to peripheral tissues are largely unknown. Here we explored the role of one rhythmic gene, Achilles, in regulating the rhythmic transcriptome in the fly head. Achilles is a clock-controlled gene in Drosophila that encodes a putative RNA-binding protein. Achilles expression is found in neurons throughout the fly brain using fluorescence in situ hybridization (FISH), and legacy data suggest it is not expressed in core clock neurons. Together, these observations argue against a role for Achilles in regulating the core clock. To assess its impact on circadian mRNA rhythms, we performed RNA sequencing (RNAseq) to compare the rhythmic transcriptomes of control flies and those with diminished Achilles expression in all neurons. Consistent with previous studies, we observe dramatic upregulation of immune response genes upon knock-down of Achilles. Furthermore, many circadian mRNAs lose their rhythmicity in Achilles knock-down flies, suggesting that a subset of the rhythmic transcriptome is regulated either directly or indirectly by Achilles. These Achilles-mediated rhythms are observed in genes involved in immune function and in neuronal signaling, including Prosap, Nemy and Jhl-21. A comparison of RNAseq data from control flies reveals that only 42.7% of clock-controlled genes in the fly brain are rhythmic in both males and females. As mRNA rhythms of core clock genes are largely invariant between the sexes, this observation suggests that sex-specific mechanisms are an important, and heretofore under-appreciated, regulator of the rhythmic transcriptome.
KW - Achilles (Achl)
KW - RNA sequencing (RNAseq)
KW - circadian rhythms
KW - clock-controlled genes (CCGs)
KW - sex specificity
UR - http://www.scopus.com/inward/record.url?scp=85062335430&partnerID=8YFLogxK
U2 - 10.1177/0748730419830845
DO - 10.1177/0748730419830845
M3 - Article
C2 - 30803307
AN - SCOPUS:85062335430
VL - 34
SP - 131
EP - 143
JO - Journal of Biological Rhythms
JF - Journal of Biological Rhythms
SN - 0748-7304
IS - 2
ER -