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.