Nocturnin, a deadenylase in Xenopus laevis retina: a mechanism for posttranscriptional control of circadian-related mRNA.
BACKGROUND
Different types of regulation are utilized to produce a robust circadian clock, including regulation at the transcriptional, posttranscriptional, and translational levels. A screen for rhythmic messages that may be involved in such circadian control identified nocturnin, a novel gene that displays high-amplitude circadian expression in the Xenopus laevis retina, with peak mRNA levels in the early night. Expression of nocturnin mRNA is confined to the clock-containing photoreceptor cell layer within the retina.


RESULTS
In these studies, we show that nocturnin removes the poly(A) tail from a synthetic RNA substrate in a process known as deadenylation. Nocturnin nuclease activity is magnesium dependent, as the addition of EDTA or mutation of the residue predicted to bind magnesium disrupts deadenylation. Substrate preference studies show that nocturnin is an exonuclease that specifically degrades the 3' poly(A) tail. While nocturnin is rhythmically expressed in the cytoplasm of the retinal photoreceptor cells, the only other described vertebrate deadenylase, PARN, is constitutively present in most retinal cells, including the photoreceptors.


CONCLUSIONS
The distinct spatial and temporal expression of nocturnin and PARN suggests that there may be specific mRNA targets of each deadenylase. Since deadenylation regulates mRNA decay and/or translational silencing, we propose that nocturnin deadenylates clock-related transcripts in a novel mechanism for posttranscriptional regulation in the circadian clock or its outputs.
Baggs
Julie E
JE
Department of Biology, NSF Center for Biological Timing, University of Virginia, Charlottesville, VA 22904-4328, USA.
Green
Carla B
CB
D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000201:enzymology*; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors; D014982:Xenopus laevis
D005095:Exoribonucleases; D005136:Eye Proteins; D008274:Magnesium; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C102804:nocturnin