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Rhythmic control of mRNA stability modulates circadian amplitude of mouse Period3 mRNA
Author(s) -
Kim SungHoon,
Lee KyungHa,
Kim DoYeon,
Kwak Eunyee,
Kim Seunghwan,
Kim KyongTai
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13027
Subject(s) - messenger rna , circadian rhythm , untranslated region , biology , microbiology and biotechnology , messenger rnp , gene expression , three prime untranslated region , translation (biology) , clock , circadian clock , gene , genetics , endocrinology
The daily oscillations observed in most living organisms are endogenously generated with a period of 24 h, and the underlying structure of periodic oscillation is an autoregulatory transcription‐translation feedback loop. The mechanisms of untranslated region ( UTR )‐mediated post‐transcriptional regulation (e.g., mRNA degradation and internal ribosomal entry site (IRES)‐mediated translation) have been suggested to fine‐tune the expression of clock genes. Mouse Period3 ( m P er3 ) is one of the paralogs of P eriod gene and its function is important in peripheral clocks and sleep physiology. m P er3 mRNA displays a circadian oscillation as well as a circadian phase‐dependent stability, while the stability regulators still remain unknown. In this study, we identify three proteins – heterogeneous nuclear ribonucleoprotein (hn RNP ) K, polypyrimidine tract‐binding protein (PTB), and hn RNP D – that bind to m P er3 mRNA 3′‐ UTR . We show that hn RNP K is a stabilizer that increases the amplitude of circadian m P er3 mRNA oscillation and hn RNP D is a destabilizer that decreases it, while PTB exhibits no effect on m P er3 mRNA expression. Our experiments describe their cytoplasmic roles for the mRNA stability regulation and the circadian amplitude formation. Moreover, our mathematical model suggests a mechanism through which post‐transcriptional mRNA stability modulation provides not only the flexibility of oscillation amplitude, but also the robustness of the period and the phase for circadian m P er3 expression.Mouse Period3 (m Per3 ) is one of well‐known clock genes. We identified three 3′‐UTR‐binding proteins that modulate the mRNA stability, and they influenced to the amplitude of circadian m Per3 mRNA oscillation. Our mathematical model not only showed the relationship between mRNA stability and its oscillation profile but provided the molecular mechanism for the robustness of the period and the phase in circadian oscillation. hnK, heterogeneous nuclear ribonucleoprotein (hnRNP) K; hnD, hnRNP D; PTB, polypyrimidine tract‐binding protein.