Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation

T.-D. Kim, J.-S. Kim, H.K. Jong, J. Myung, H.-D. Chae, K.-C. Woo, K.J. Sung, D.-S. Koh, K.-T. Kim

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase [AANAT]) is the key enzyme in melatonin synthesis regulated by circadian rhythm. To date, our understanding of the oscillatory mechanism of melatonin has been limited to autoregulatory transcriptional and posttranslational regulations of AANAT mRNA. In this study, we identify three proteins from pineal glands that associate with cis-acting elements within species-specific AANAT 3′ untranslated regions to mediate mRNA degradation. These proteins include heterogeneous nuclear ribonucleoprotein R (hnRNP R), hnRNP Q, and hnRNP L. Their RNA-destabilizing function was determined by RNA interference and overexpression approaches. Expression patterns of these factors in pineal glands display robust circadian rhythm. The enhanced levels detected after midnight correlate with an abrupt decline in AANAT mRNA level. A mathematical model for the AANAT mRNA profile and its experimental evidence with rat pinealocytes indicates that rhythmic AANAT mRNA degradation mediated by hnRNP R, hnRNP Q, and hnRNP L is a key process in the regulation of its circadian oscillation. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Original languageEnglish
Pages (from-to)3232-3246
Number of pages15
JournalMolecular and Cellular Biology
Volume25
Issue number8
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • cis acting element
  • heterogeneous nuclear ribonucleoprotein
  • heterogeneous nuclear ribonucleoprotein L
  • heterogeneous nuclear ribonucleoprotein Q
  • heterogeneous nuclear ribonucleoprotein R
  • messenger RNA
  • serotonin n acetyltransferase
  • unclassified drug
  • 3' untranslated region
  • animal cell
  • animal experiment
  • animal tissue
  • article
  • circadian rhythm
  • controlled study
  • gene overexpression
  • mathematical model
  • nonhuman
  • nucleotide sequence
  • oscillation
  • pineal body
  • pinealocyte
  • priority journal
  • protein analysis
  • rat
  • RNA degradation
  • RNA interference
  • RNA stability
  • species difference
  • 3' Untranslated Regions
  • Animals
  • Arylalkylamine N-Acetyltransferase
  • Base Sequence
  • Circadian Rhythm
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Molecular Sequence Data
  • Pineal Gland
  • Rats
  • RNA Stability
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins

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