Regulation of the cycling of timeless (tim) RNA

Journal of Neurobiology
G K WangAmita Sehgal

Abstract

Circadian rhythms in Drosophila depend upon expression of the timeless (tim) and period (per) genes, which encode interacting components of the endogenous clock. These two clock genes show a robust circadian oscillation in transcription rate as well as RNA and protein levels. Transcriptional activation of both genes requires the basic helix-loop-helix (bHLH) PAS transcription factors dCLOCK (dCLK) and CYCLE (CYC), which bind E-box elements. We investigated the role of E-box elements in regulating behavioral rhythmicity and tim gene expression. We show that mutation of the upstream E-box in the tim gene prevents the rescue by tim cDNA sequences of the arrhythmic tim(01) phenotype. RNA encoded by this mutated tim transgene fails to cycle and is expressed at low levels. While a tim transgene carrying a wild-type E-box restores behavioral rhythms, tim RNA levels are intermediate to those of the mutant E-box transgenic lines and wild type, and do not display high amplitude cycling. On the other hand, high-amplitude RNA cycling was consistently obtained with a tim transgene that contains genomic, rather than cDNA, sequences. To identify additional sequences that may be required for tim cycling, we investigated the role of an E-box in...Continue Reading

References

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Citations

Jun 7, 2002·Current Opinion in Neurobiology·Garrick K Wang, Amita Sehgal
Feb 12, 2005·Bioinformatics·Nobukazu Ohki, Masatoshi Hagiwara
Jul 26, 2011·Nucleic Acids Research·Do-Yeon KimKyong-Tai Kim
Jun 21, 2007·Genes & Development·Sebastian KadenerMichael Rosbash
Apr 5, 2013·PLoS Genetics·Apiruck WatthanasurorotIrene Söderhäll
Apr 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Allan C FroehlichJay C Dunlap
Aug 29, 2014·Proceedings. Biological Sciences·Tadahiro GodaHerman Wijnen
Nov 10, 2004·Journal of Biological Rhythms·Paul E Hardin
May 11, 2006·The Journal of Biological Chemistry·Eunyee KwakKyong-Tai Kim
Jul 20, 2002·The Journal of Biological Chemistry·Estela MuñozRuben Baler
Jul 19, 2003·Chronobiology International·Estela Muñoz, Ruben Baler
Jul 21, 2001·Seminars in Cell & Developmental Biology·J Blau
Sep 6, 2005·Current Biology : CB·Paul E Hardin

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