lishes a conserved mechanism for circadian clock
regulation. EMBO J 22:4421–4430. https://doi.org/
10.1093/emboj/cdg425
He Q, Shu H, Cheng P et al (2005) Light-independent
phosphorylation of WHITE COLLAR-1 regulates
its function in the Neurospora circadian negative
feedback loop. J Biol Chem 280:17526–17532.
https://doi.org/10.1074/jbc.M414010200
He Q, Cha J, He Q et al (2006) CKI and CKII mediate the
FREQUENCY-dependent phosphorylation of the
WHITE COLLAR complex to close the Neurospora
circadian negative feedback loop. Genes Dev
20:2552–2565.
https://doi.org/10.1101/
gad.1463506
Heintzen C, Loros JJ, Dunlap JC (2001) The PAS protein
VIVID defines a clock-associated feedback loop
that represses light input, modulates gating, and
regulates clock resetting. Cell 104:453–464. https://
doi.org/10.1016/S0092-8674(01)00232-X
Hevia MA, Canessa P, Mu ¨ller-Esparza H, Larrondo LF
(2015) A circadian oscillator in the fungus Botrytis
cinerea regulates virulence when infecting Arabidopsis thaliana. Proc Natl Acad Sci 112:8744–8749
Hevia MA, Canessa P, Larrondo LF (2016) Circadian
clocks and the regulation of virulence in fungi:
getting up to speed. Semin Cell Dev Biol 57:147–
155. https://doi.org/10.1016/j.semcdb.2016.03.021
Hirano A, Fu Y-H, Pta ´c ˇek LJ (2016) The intricate dance
of post-translational modifications in the rhythm
of life. Nat Struct Mol Biol 23:1053
Hong CI, Ruoff P, Loros JJ, Dunlap JC (2008) Closing
the circadian negative feedback loop: FRQdependent clearance of WC-1 from the nucleus.
Genes Dev 22:3196–3204. https://doi.org/10.1101/
gad.1706908
Hong CI, Zamborszky J, Baek M et al (2014) Circadian
rhythms synchronize mitosis in Neurospora
crassa. Proc Natl Acad Sci 111:1397–1402. https://
doi.org/10.1073/pnas.1319399111
Huang G, Chen S, Li S et al (2007) Protein kinase a and
casein kinases mediate sequential phosphorylation
events in the circadian negative feedback loop.
Genes Dev 21:3283–3295. https://doi.org/10.1101/
gad.1610207
Huang G, He Q, Guo J et al (2013) The Ccr4-not protein
complex regulates the phase of the Neurospora
circadian clock by controlling WHITE COLLAR
protein stability and activity. J Biol Chem
288:31002–31009.
https://doi.org/10.1074/jbc.
M113.494120
Hunt SM, Thompson S, Elvin M, Heintzen C (2010)
VIVID interacts with the WHITE COLLAR complex and FREQUENCY-interacting RNA helicase
to alter light and clock responses in Neurospora.
Proc Natl Acad Sci 107:16709–16714. https://doi.
org/10.1073/pnas.1009474107
Hurley JM, Larrondo LF, Loros JJ, Dunlap JC (2013)
Conserved RNA helicase FRH acts nonenzymatically to support the intrinsically disordered Neurospora clock protein FRQ. Mol Cell 52:832–843.
https://doi.org/10.1016/j.molcel.2013.11.005
Hurley JM, Dasgupta A, Emerson JM et al (2014) Analysis of clock-regulated genes in Neurospora reveals
widespread posttranscriptional control of metabolic potential. Proc Natl Acad Sci 111:16995–
17002. https://doi.org/10.1073/pnas.1418963111
Hurley JM, Loros JJ, Dunlap JC (2016a) Circadian
oscillators: around the transcription–translation
feedback loop and on to output. Trends Biochem
Sci
41:834–846.
https://doi.org/10.1016/j.
tibs.2016.07.009
Hurley JM, Loros JJ, Dunlap JC (2016b) The circadian
system as an organizer of metabolism. Fungal
Genet Biol 90:39–43. https://doi.org/10.1016/j.
fgb.2015.10.002
Hurley JM, Jankowski MS, De los Santos H et al (2018)
Circadian proteomic analysis uncovers mechanisms of post-transcriptional regulation in metabolic pathways. Cell Syst 7:613. https://doi.org/
10.1016/j.cels.2018.10.014
Hut RA, Beersma DGM (2011) Evolution of timekeeping mechanisms: early emergence and adaptation to photoperiod. Philos Trans R Soc Lond
Ser B Biol Sci 366:2141–2154. https://doi.org/
10.1098/rstb.2010.0409
Idnurm A, Verma S, Corrochano LM (2010) A glimpse
into the basis of vision in the kingdom Mycota.
Fungal Genet Biol 47:881–892. https://doi.org/
10.1016/j.fgb.2010.04.009
Janich P, Arpat AB, Castelo-Szekely V et al (2015)
Ribosome profiling reveals the rhythmic liver
translatome and circadian clock regulation by
upstream open reading frames. Genome Res
25:1848–1859.
https://doi.org/10.1101/
gr.195404.115
Johnson CH, Elliott J, Russell F et al (2004) Fundamental properties of circadian rhythms. In: Dunlap JC,
Loros JJ, DeCoursey PJ (eds) Chronobiology:
biological timekeeping. Sinauer Associates, Sunderland, MA, pp 67–106
Jonkers W, Rep M (2009) Lessons from fungal F-box
proteins. Eukaryot Cell 8:677–695. https://doi.org/
10.1128/EC.00386-08
Kafri M, Metzl-Raz E, Jona G, Barkai N (2016) The cost
of protein production. Cell Rep 14:22–31. https://
doi.org/10.1016/j.celrep.2015.12.015
Ko HW, Jiang J, Edery I (2002) Role for Slimb in the
degradation of Drosophila period protein phosphorylated by Doubletime. Nature 420:673
Koike N, Yoo S-H, Huang H-C et al (2012) Transcriptional architecture and chromatin landscape of the
core circadian clock in mammals. Science 338:349–
354. https://doi.org/10.1126/science.1226339
Kojima S, Shingle DL, Green CB (2011) Posttranscriptional control of circadian rhythms. J
Cell Sci 124:311–320. https://doi.org/10.1242/
jcs.065771
Kramer C, Loros JJ, Dunlap JC, Crosthwaite SK (2003)
Role for antisense RNA in regulating circadian
clock function in Neurospora crassa. Nature
421:948
4 From Genetics to Molecular Oscillations: The Circadian Clock in Neurospora crassa
99
regulation. EMBO J 22:4421–4430. https://doi.org/
10.1093/emboj/cdg425
He Q, Shu H, Cheng P et al (2005) Light-independent
phosphorylation of WHITE COLLAR-1 regulates
its function in the Neurospora circadian negative
feedback loop. J Biol Chem 280:17526–17532.
https://doi.org/10.1074/jbc.M414010200
He Q, Cha J, He Q et al (2006) CKI and CKII mediate the
FREQUENCY-dependent phosphorylation of the
WHITE COLLAR complex to close the Neurospora
circadian negative feedback loop. Genes Dev
20:2552–2565.
https://doi.org/10.1101/
gad.1463506
Heintzen C, Loros JJ, Dunlap JC (2001) The PAS protein
VIVID defines a clock-associated feedback loop
that represses light input, modulates gating, and
regulates clock resetting. Cell 104:453–464. https://
doi.org/10.1016/S0092-8674(01)00232-X
Hevia MA, Canessa P, Mu ¨ller-Esparza H, Larrondo LF
(2015) A circadian oscillator in the fungus Botrytis
cinerea regulates virulence when infecting Arabidopsis thaliana. Proc Natl Acad Sci 112:8744–8749
Hevia MA, Canessa P, Larrondo LF (2016) Circadian
clocks and the regulation of virulence in fungi:
getting up to speed. Semin Cell Dev Biol 57:147–
155. https://doi.org/10.1016/j.semcdb.2016.03.021
Hirano A, Fu Y-H, Pta ´c ˇek LJ (2016) The intricate dance
of post-translational modifications in the rhythm
of life. Nat Struct Mol Biol 23:1053
Hong CI, Ruoff P, Loros JJ, Dunlap JC (2008) Closing
the circadian negative feedback loop: FRQdependent clearance of WC-1 from the nucleus.
Genes Dev 22:3196–3204. https://doi.org/10.1101/
gad.1706908
Hong CI, Zamborszky J, Baek M et al (2014) Circadian
rhythms synchronize mitosis in Neurospora
crassa. Proc Natl Acad Sci 111:1397–1402. https://
doi.org/10.1073/pnas.1319399111
Huang G, Chen S, Li S et al (2007) Protein kinase a and
casein kinases mediate sequential phosphorylation
events in the circadian negative feedback loop.
Genes Dev 21:3283–3295. https://doi.org/10.1101/
gad.1610207
Huang G, He Q, Guo J et al (2013) The Ccr4-not protein
complex regulates the phase of the Neurospora
circadian clock by controlling WHITE COLLAR
protein stability and activity. J Biol Chem
288:31002–31009.
https://doi.org/10.1074/jbc.
M113.494120
Hunt SM, Thompson S, Elvin M, Heintzen C (2010)
VIVID interacts with the WHITE COLLAR complex and FREQUENCY-interacting RNA helicase
to alter light and clock responses in Neurospora.
Proc Natl Acad Sci 107:16709–16714. https://doi.
org/10.1073/pnas.1009474107
Hurley JM, Larrondo LF, Loros JJ, Dunlap JC (2013)
Conserved RNA helicase FRH acts nonenzymatically to support the intrinsically disordered Neurospora clock protein FRQ. Mol Cell 52:832–843.
https://doi.org/10.1016/j.molcel.2013.11.005
Hurley JM, Dasgupta A, Emerson JM et al (2014) Analysis of clock-regulated genes in Neurospora reveals
widespread posttranscriptional control of metabolic potential. Proc Natl Acad Sci 111:16995–
17002. https://doi.org/10.1073/pnas.1418963111
Hurley JM, Loros JJ, Dunlap JC (2016a) Circadian
oscillators: around the transcription–translation
feedback loop and on to output. Trends Biochem
Sci
41:834–846.
https://doi.org/10.1016/j.
tibs.2016.07.009
Hurley JM, Loros JJ, Dunlap JC (2016b) The circadian
system as an organizer of metabolism. Fungal
Genet Biol 90:39–43. https://doi.org/10.1016/j.
fgb.2015.10.002
Hurley JM, Jankowski MS, De los Santos H et al (2018)
Circadian proteomic analysis uncovers mechanisms of post-transcriptional regulation in metabolic pathways. Cell Syst 7:613. https://doi.org/
10.1016/j.cels.2018.10.014
Hut RA, Beersma DGM (2011) Evolution of timekeeping mechanisms: early emergence and adaptation to photoperiod. Philos Trans R Soc Lond
Ser B Biol Sci 366:2141–2154. https://doi.org/
10.1098/rstb.2010.0409
Idnurm A, Verma S, Corrochano LM (2010) A glimpse
into the basis of vision in the kingdom Mycota.
Fungal Genet Biol 47:881–892. https://doi.org/
10.1016/j.fgb.2010.04.009
Janich P, Arpat AB, Castelo-Szekely V et al (2015)
Ribosome profiling reveals the rhythmic liver
translatome and circadian clock regulation by
upstream open reading frames. Genome Res
25:1848–1859.
https://doi.org/10.1101/
gr.195404.115
Johnson CH, Elliott J, Russell F et al (2004) Fundamental properties of circadian rhythms. In: Dunlap JC,
Loros JJ, DeCoursey PJ (eds) Chronobiology:
biological timekeeping. Sinauer Associates, Sunderland, MA, pp 67–106
Jonkers W, Rep M (2009) Lessons from fungal F-box
proteins. Eukaryot Cell 8:677–695. https://doi.org/
10.1128/EC.00386-08
Kafri M, Metzl-Raz E, Jona G, Barkai N (2016) The cost
of protein production. Cell Rep 14:22–31. https://
doi.org/10.1016/j.celrep.2015.12.015
Ko HW, Jiang J, Edery I (2002) Role for Slimb in the
degradation of Drosophila period protein phosphorylated by Doubletime. Nature 420:673
Koike N, Yoo S-H, Huang H-C et al (2012) Transcriptional architecture and chromatin landscape of the
core circadian clock in mammals. Science 338:349–
354. https://doi.org/10.1126/science.1226339
Kojima S, Shingle DL, Green CB (2011) Posttranscriptional control of circadian rhythms. J
Cell Sci 124:311–320. https://doi.org/10.1242/
jcs.065771
Kramer C, Loros JJ, Dunlap JC, Crosthwaite SK (2003)
Role for antisense RNA in regulating circadian
clock function in Neurospora crassa. Nature
421:948
4 From Genetics to Molecular Oscillations: The Circadian Clock in Neurospora crassa
99