Circadian amplitude of cryptochrome 1 is modulated by mRNA stability regulation via cytoplasmic hnRNP D oscillation.
The mammalian circadian rhythm is observed not only at the suprachiasmatic nucleus, a master pacemaker, but also throughout the peripheral tissues. Its conserved molecular basis has been thought to consist of intracellular transcriptional feedback loops of key clock genes. However, little is known about posttranscriptional regulation of these genes. In the present study, we investigated the role of the 3'-untranslated region (3'UTR) of the mouse cryptochrome 1 (mcry1) gene at the posttranscriptional level. Mature mcry1 mRNA has a 610-nucleotide 3'UTR and mediates its own degradation. The middle part of the 3'UTR contains a destabilizing cis-acting element. The deletion of this element led to a dramatic increase in mRNA stability, and heterogeneous nuclear ribonucleoprotein D (hnRNP D) was identified as an RNA binding protein responsible for this effect. Cytoplasmic hnRNP D levels displayed a pattern that was reciprocal to the mcry1 oscillation. Knockdown of hnRNP D stabilized mcry1 mRNA and resulted in enhancement of the oscillation amplitude and a slight delay of the phase. Our results suggest that hnRNP D plays a role as a fine regulator contributing to the mcry1 mRNA turnover rate and the modulation of circadian rhythm.
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790784, South Korea.
Kyung-Chul
KC
Woo
Dae-Cheong
DC
Ha
Kyung-Ha
KH
Lee
Do-Yeon
DY
Kim
Tae-Don
TD
Kim
Kyong-Tai
KT
Kim
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002940:Circadian Rhythm; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology*
D020413:3' Untranslated Regions; C538964:Cry1 protein, mouse; D056931:Cryptochromes; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger