Linked Life Data

19228794

Source:http://linkedlifedata.com/resource/pubmed/id/19228794

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-4-28
pubmed:abstractText
Circadian rhythms are observed in nearly all aspects of physiology and behavior. In mammals, such biological rhythms are supported by a complex network of self-sustained transcriptional loops and posttranslational modifications, which regulate timely controlled production and degradation of critical factors on a 24-h basis. Among these factors, the orphan nuclear receptor rev-erbalpha plays an essential role by linking together positive and negative regulatory loops. As an essential part of the circadian core clock mechanism, REV-ERBalpha expression shows a precisely scheduled oscillation reflecting the tight control of its production and degradation. In previous studies, we identified two alternative transcripts encoding two protein variants referred to as REV-ERBalpha1 and -alpha2. Interestingly, recent work identified structural elements present only in REV-ERBalpha1 that controls its turnover and thereby influences circadian oscillations. In the present work, we comparatively analyze the two variants and show that REV-ERBalpha2 exhibits a half-life incompatible with a circadian function, suggesting that this variant exerts different biological functions. However, our comparative study clearly indicates undistinguishable DNA-binding properties and transcriptional repression activity as well as a similar regulation mechanism. The only consistent difference appears to be the relative expression level of the two transcripts, rev-erbalpha1 being one to 100 times more expressed than alpha2 depending on tissue and circadian time. Taking this finding into consideration, we reassessed REV-ERBalpha2 turnover and were able to show that this variant exhibits a reduced half-life when coexpressed with REV-ERBalpha1. We propose that the relative expression levels of the two REV-ERBalpha variants fine-tune the circadian period length by regulating REV-ERBalpha half-life.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
630-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19228794-Animals, pubmed-meshheading:19228794-Blotting, Western, pubmed-meshheading:19228794-COS Cells, pubmed-meshheading:19228794-Cercopithecus aethiops, pubmed-meshheading:19228794-Circadian Rhythm, pubmed-meshheading:19228794-Computational Biology, pubmed-meshheading:19228794-DNA-Binding Proteins, pubmed-meshheading:19228794-Electrophoretic Mobility Shift Assay, pubmed-meshheading:19228794-Gene Expression Regulation, pubmed-meshheading:19228794-Immunoprecipitation, pubmed-meshheading:19228794-Male, pubmed-meshheading:19228794-Mice, pubmed-meshheading:19228794-Nuclear Receptor Subfamily 1, Group D, Member 1, pubmed-meshheading:19228794-Promoter Regions, Genetic, pubmed-meshheading:19228794-Protein Isoforms, pubmed-meshheading:19228794-Protein Multimerization, pubmed-meshheading:19228794-RNA, Messenger, pubmed-meshheading:19228794-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:19228794-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19228794-Transcription, Genetic
pubmed:year
2009
pubmed:articleTitle
Rev-erbalpha2 mRNA encodes a stable protein with a potential role in circadian clock regulation.
pubmed:affiliation
Molecular Zoology Group, Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS, INRA, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't