RRC ID 47918
著者 Lee J, Yoo E, Lee H, Park K, Hur JH, Lim C.
タイトル LSM12 and ME31B/DDX6 Define Distinct Modes of Posttranscriptional Regulation by ATAXIN-2 Protein Complex in Drosophila Circadian Pacemaker Neurons.
ジャーナル Mol Cell
Abstract ATAXIN-2 (ATX2) has been implicated in human neurodegenerative diseases, yet it remains elusive how ATX2 assembles specific protein complexes to execute its physiological roles. Here we employ the posttranscriptional co-activator function of Drosophila ATX2 to demonstrate that LSM12 and ME31B/DDX6 are two ATX2-associating factors crucial for sustaining circadian rhythms. LSM12 acts as a molecular adaptor for the recruitment of TWENTY-FOUR (TYF) to ATX2. The ATX2-LSM12-TYF complex thereby stimulates TYF-dependent translation of the rate-limiting clock gene period (per) to maintain 24 hr periodicity in circadian behaviors. In contrast, ATX2 contributes to NOT1-mediated gene silencing and associates with NOT1 in a ME31B/DDX6-dependent manner. The ME31B/DDX6-NOT1 complex does not affect PER translation but supports high-amplitude behavioral rhythms along with ATX2, indicating a PER-independent clock function of ATX2. Taken together, these data suggest that the ATX2 complex may switch distinct modes of posttranscriptional regulation through its associating factors to control circadian clocks and ATX2-related physiology.
巻・号 66(1)
ページ 129-140.e7
公開日 2017-4-6
DOI 10.1016/j.molcel.2017.03.004
PII S1097-2765(17)30171-5
PMID 28388438
MeSH Animals Animals, Genetically Modified Ataxin-2 / genetics Ataxin-2 / metabolism* Behavior, Animal* Carrier Proteins / genetics Carrier Proteins / metabolism Cell Line Circadian Clocks* Circadian Rhythm* Circadian Rhythm Signaling Peptides and Proteins / genetics Circadian Rhythm Signaling Peptides and Proteins / metabolism* DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / enzymology* Drosophila melanogaster / genetics Genotype Locomotion* Multiprotein Complexes Mutation Neurons / enzymology* Period Circadian Proteins / genetics Period Circadian Proteins / metabolism Phenotype RNA Interference* RNA-Binding Proteins Signal Transduction Time Factors Transfection
IF 15.584
引用数 15
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ショウジョウバエ 4916R-2