Psychiatry related information on Per3

• Locomotor activity rhythms in mPER3-deficient mice were grossly normal, but the circadian cycle length was significantly (0.5 h) shorter than that in controls [1].

High impact information on Per3

• Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified [2].
• Here we report that nuclear translocation of mPER1 and mPER2 (1) involves physical interactions with mPER3, (2) is accelerated by serum treatment, and (3) still occurs in mCry1/mCry2 double-deficient cells lacking a functional biological clock [3].
• The mPER3 amino acid sequence predicts the presence of a cytoplasmic localization domain (CLD) and a nuclear localization signal (NLS) [3].
• The three mammalian PER proteins share several regions of sequence homology, and each contains a protein dimerization PAS domain. mPer3 RNA levels oscillate in the suprachiasmatic nuclei (SCN) and eyes [4].
• Cycling expression of mPer3 was also found outside the SCN in the organum vasculosum lamina terminalis (OVLT), a potentially key region regulating rhythmic gonadotropin production and pyrogen-induced febrile phenomena [5].

Biological context of Per3

• The results demonstrate that mPer3 is not necessary for circadian rhythms in mice [1].
• We conclude that hPer4 and RmPer4 are pseudogenes and descended from the retrotransposition of an ancestral Per3 gene [6].
• The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway [7].
• Functional analysis of dominant-negative mPER1 variants designed either to sequester mPER3 to the cytoplasm or to inhibit nuclear export of mCRY1/2 in synchronized, stably transfected fibroblasts suggests that mPER1-mediated export of mCRY1/2 defines an important new element of the core clock machinery in vertebrates [8].
• Our results indicate that mPer3 3'-UTR-mediated mRNA decay plays an essential role in mRNA cycling and provide direct evidence for post-transcriptional control of circadian mRNA oscillations [9].

Anatomical context of Per3

• 1. Per2 and Per3 genes were both localized to microchromosomes. qClock mRNA was expressed throughout the day, while qPer2 and qPer3 showed robust circadian oscillation in the eye and the pineal gland [10].
• Whereas mPer1 and mPer2 are light-inducible in clock neurons of the hypothalamic suprachiasmatic nucleus, mPer3 is not [11].
• There was no difference in the mPer3 rhythms in either the SCN or the cerebral cortex between the split and unsplit mice [12].
• Nuclear import of mPER3 in Xenopus oocytes and HeLa cells requires complex formation with mPER1 [13].
• Eight genes (mBmal1, mNpas2, mRev-erbalpha, mDbp, mRev-erbbeta, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak) showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock [14].

Associations of Per3 with chemical compounds

• These results indicate that the circadian oscillations of mPer1, mPer2 and mPer3 in the SCN are not related to the rhythm splitting of CS mice [12].

Regulatory relationships of Per3

• Moreover, CKIepsilon and CKIdelta are able to induce nuclear translocation of mPer3, which requires its nuclear localization signal [7].

Other interactions of Per3

• The mPER3 protein shows approximately 37% amino acid identity with mPER1 and mPER2 proteins [4].
• Overall, qCLOCK, qPER2 and qPER3 showed approximately 79%, approximately 46% and approximately 33% amino acid identity to mCLOCK, mPER2, mPER3, respectively [10].
• In vitro studies with chimeric proteins suggest that the inability of mPER3 to support circadian clock function results in part from lack of direct and stable interaction with casein kinase Iepsilon (CKIepsilon) [15].
• Expressions of several genes such as Per3 and Rad51ap1 displayed inter-strain differences [16].

References