A Caltech Library Service

Identification of novel genes involved in light-dependent CRY degradation through a genome-wide RNAi screen

Sathyanarayanan, Sriram and Zheng, Xiangzhong and Kumar, Shailes and Chen, Chun-Hong and Chen, Dechun and Hay, Bruce and Sehgal, Amita (2008) Identification of novel genes involved in light-dependent CRY degradation through a genome-wide RNAi screen. Genes and Development, 22 (11). pp. 1522-1533. ISSN 0890-9369. PMCID PMC2418588. doi:10.1101/gad.1652308.

[img] PDF - Published Version
Creative Commons Attribution.

[img] MS Word - Supplemental Material
See Usage Policy.

[img] MS Word - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


Circadian clocks regulate many different physiological processes and synchronize these to environmental light:dark cycles. In Drosophila, light is transmitted to the clock by a circadian blue light photoreceptor CRYPTOCHROME (CRY). In response to light, CRY promotes the degradation of the circadian clock protein TIMELESS (TIM) and then is itself degraded. To identify novel genes involved in circadian entrainment, we performed an unbiased genome-wide screen in Drosophila cells using a sensitive and quantitative assay that measures light-induced degradation of CRY. We systematically knocked down the expression of ∼21,000 genes and identified those that regulate CRY stability. These genes include ubiquitin ligases, signal transduction molecules, and redox molecules. Many of the genes identified in the screen are specific for CRY degradation and do not affect degradation of the TIM protein in response to light, suggesting that, for the most part, these two pathways are distinct. We further validated the effect of three candidate genes on CRY stability in vivo by assaying flies mutant for each of these genes. This work identifies a novel regulatory network involved in light-dependent CRY degradation and demonstrates the power of a genome-wide RNAi approach for understanding circadian biology.

Item Type:Article
Related URLs:
URLURL TypeDescription Information CentralArticle
Additional Information:© 2008 by Cold Spring Harbor Laboratory Press. Received January 16, 2008; revised version accepted April 3, 2008. We thank members of the DRSC, especially Bernard Mathey-Prevot, Susan Armknecht, Matthew Booker, and Norbert Perrimon for providing the genome-wide RNAi library and for help with RNAi screening; Patrick Emery for the anti-CRY antibody; Tadashi Uemura for ssh fly stocks; Yanshan Fang for the pIZ-myc-cry plasmid; Kent Nybakkan for the PolIII-rluc plasmid; members of the Perrimon laboratory for help with the assay set-up; and Kyunghee Koh and Susan Harbison for help with data analysis. S.S. and X.Z. were supported in part by NIH grant NS048471.
Funding AgencyGrant Number
Subject Keywords:RNAi; circadian rhythms; clock proteins; degradation; photoreceptors
Issue or Number:11
PubMed Central ID:PMC2418588
Record Number:CaltechAUTHORS:20200505-142412827
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103005
Deposited By: Tony Diaz
Deposited On:05 May 2020 21:53
Last Modified:16 Nov 2021 18:17

Repository Staff Only: item control page