PMID- 30803307 OWN - NLM STAT- MEDLINE DCOM- 20200519 LR - 20200519 IS - 1552-4531 (Electronic) IS - 0748-7304 (Linking) VI - 34 IP - 2 DP - 2019 Apr TI - Achilles-Mediated and Sex-Specific Regulation of Circadian mRNA Rhythms in Drosophila. PG - 131-143 LID - 10.1177/0748730419830845 [doi] 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. FAU - Li, Jiajia AU - Li J AD - Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA. FAU - Yu, Renee Yin AU - Yu RY AD - Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada. FAU - Emran, Farida AU - Emran F AD - Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada. FAU - Chen, Brian E AU - Chen BE AD - Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada. AD - Departments of Medicine and Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. FAU - Hughes, Michael E AU - Hughes ME AD - Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA. LA - eng GR - R21 AR069266/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190225 PL - United States TA - J Biol Rhythms JT - Journal of biological rhythms JID - 8700115 RN - 0 (Drosophila Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) SB - IM MH - Animals MH - Circadian Clocks/genetics MH - Circadian Rhythm/*genetics MH - Drosophila/*genetics/physiology MH - Drosophila Proteins/*genetics MH - Female MH - *Gene Expression Regulation MH - Male MH - Neurons/physiology MH - RNA, Messenger/*genetics MH - RNA-Binding Proteins/genetics MH - Sequence Analysis, RNA MH - *Sex Factors MH - Transcriptome MH - Up-Regulation OTO - NOTNLM OT - RNA sequencing (RNAseq) OT - circadian rhythms OT - clock-controlled genes (CCGs) OT - sex specificity EDAT- 2019/02/26 06:00 MHDA- 2020/05/20 06:00 CRDT- 2019/02/27 06:00 PHST- 2019/02/26 06:00 [pubmed] PHST- 2020/05/20 06:00 [medline] PHST- 2019/02/27 06:00 [entrez] AID - 10.1177/0748730419830845 [doi] PST - ppublish SO - J Biol Rhythms. 2019 Apr;34(2):131-143. doi: 10.1177/0748730419830845. Epub 2019 Feb 25.