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

59 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

Fingerprint

Arylalkylamine N-Acetyltransferase
RNA Stability
Heterogeneous-Nuclear Ribonucleoproteins
Maintenance
Heterogeneous-Nuclear Ribonucleoprotein L
Pineal Gland
Melatonin
Circadian Rhythm
Messenger RNA
3' Untranslated Regions
RNA Interference
Microbiology
Proteins
Theoretical Models
RNA

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

Cite this

Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation. / Kim, T.-D.; Kim, J.-S.; Jong, H.K.; Myung, J.; Chae, H.-D.; Woo, K.-C.; Sung, K.J.; Koh, D.-S.; Kim, K.-T.

In: Molecular and Cellular Biology, Vol. 25, No. 8, 2005, p. 3232-3246.

Research output: Contribution to journalArticle

Kim, T.-D. ; Kim, J.-S. ; Jong, H.K. ; Myung, J. ; Chae, H.-D. ; Woo, K.-C. ; Sung, K.J. ; Koh, D.-S. ; Kim, K.-T. / Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 8. pp. 3232-3246.
@article{bf84b623883e434f83ed294d8b329adc,
title = "Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation",
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 {\circledC} 2005, American Society for Microbiology. All Rights Reserved.",
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",
author = "T.-D. Kim and J.-S. Kim and H.K. Jong and J. Myung and H.-D. Chae and K.-C. Woo and K.J. Sung and D.-S. Koh and K.-T. Kim",
note = "引用次數:56 Export Date: 18 September 2018 CODEN: MCEBD 通訊地址: Kim, K.-T.; National Research Laboratory, Department of Life Science, Pohang Univ. of Sci. and Technology, San 31 Hyoja-Dong, Pohang, Kyung-Buk 790-784, South Korea; 電子郵件: ktk@postech.ac.kr 分析序列編號: GENBANK: AF004108, AF092100, AKK59705, AY184814, NM_001533, NM_005817, NM_017008, NM_177509, U29663, U38306, U46502, U46661, XM_008139; 化學物質/CAS: 3' Untranslated Regions; Arylalkylamine N-Acetyltransferase, EC 2.3.1.87; Heterogeneous-Nuclear Ribonucleoproteins; RNA, Messenger; RNA, Small Interfering; RNA-Binding Proteins 參考文獻: Andreason, G.L., Evans, G.A., Introduction and expression of DNA molecules in eukaryotic cells by electroporation (1988) BioTechniques, 6, pp. 650-660; Baler, R., Covington, S., Klein, D.C., The rat arylalkylamine N-acetyltransferase gene promoter: cAMP activation via a cAMP-responsive element-CCAAT complex (1997) J. Biol. Chem., 272, pp. 6979-6985; Bernard, M., Iuvone, P.M., Cassone, V.M., Roseboom, P.H., Coon, S.L., Klein, D.C., Avian melatonin synthesis: Photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina (1997) J. Neurochem., 68, pp. 213-224; Borjigin, J., Wang, M.M., Snyder, S.H., Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal gland (1995) Nature, 378, pp. 783-785; Chae, H.D., Park, T.J., Lee, Y.K., Lee, T.G., Kim, K.T., Rapid and simple measurement of serotonin N-acetyltransferase activity by liquid biphasic diffusion assay (1999) Neurochem. Int., 35, pp. 447-451; Coon, S.L., Roseboom, P.H., Baler, R., Weller, J.L., Namboodiri, M.A., Koonin, E.V., Klein, D.C., Pineal serotonin N-acetyltransferase: Expression cloning and molecular analysis (1995) Science, 270, pp. 1681-1683; Coon, S.L., Del Olmo, E., Young III, W.S., Klein, D.C., Melatonin synthesis enzymes in Macaca mulatta: Focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87) (2002) J. Clin. Endocrinol. Metab., 87, pp. 4699-4706; Craft, C.M., Murage, J., Brown, B., Zhan-Poe, X., Bovine arylalkylamine N-acetyltransferase activity correlated with mRNA expression in pineal and retina (1999) Brain Res. Mol. Brain Res., 65, pp. 44-51; Dreyfuss, G., Kim, V.N., Kataoka, N., Messenger-RNA-binding proteins and the messages they carry (2002) Nat. Rev. Mol. Cell Biol., 3, pp. 195-205; Dunlap, J.C., Molecular bases for circadian clocks (1999) Cell, 96, pp. 271-290; Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., Tuschl, T., Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells (2000) Nature, 411, pp. 494-498; Forger, D.B., Peskin, C.S., A detailed predictive model of the mammalian circadian clock (2003) Proc. Natl. Acad. Sci. USA, 100, pp. 14806-14811; Foulkes, N.S., Borjigin, J., Snyder, S.H., Sassone-Corsi, P., Transcriptional control of circadian hormone synthesis via the CREM feedback loop (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 14140-14145; Foulkes, N.S., Borjigin, J., Snyder, S.H., Sassone-Corsi, P., Rhythmic transcription: The molecular basis of circadian melatonin synthesis (1997) Trends Neurosci., 20, pp. 487-492; Ganguly, S., Coon, S.L., Klein, D.C., Control of melatonin synthesis in the mammalian pineal gland: The critical role of serotonin acetylation (2002) Cell Tissue Res., 309, pp. 127-137; Gastel, J.A., Roseboom, P.H., Rinaldi, P.A., Weller, J.L., Klein, D.C., Melatonin production: Proteasomal proteolysis in serotonin N-acetyltransferase regulation (1998) Science, 279, pp. 1358-1360; Gauer, F., Poierl, V.J., Garidou, M.L., Simonneaux, V., Pevet, P., Molecular cloning of the arylalkylamine N-acetyltransferase and daily variations of its mRNA expression in the Syrian hamster pineal gland (1999) Brain Res. Mol. Brain Res., 71, pp. 87-95; Goldbeter, A., Computational approaches to cellular rhythms (2002) Nature, 420, pp. 238-245; Goodwin, B.C., Oscillatory behavior in enzymatic control processes (1965) Adv. Enzyme Regul., 3, pp. 425-438; Grosset, C., Chen, C.Y., Xu, N., Sonenberg, N., Jacquemin-Sablon, H., Shyu, A.B., A mechanism for translationally coupled mRNA turnover: Interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex (2000) Cell, 103, pp. 29-40; Hahm, B., Cho, O.H., Kim, J.E., Kim, Y.K., Kim, J.H., Oh, Y.L., Jang, S.K., Polypyrimidine tract-binding protein interacts with hnRNP L. (1998) FEBS Lett., 425, pp. 401-406; Hardin, P.E., Hall, J.C., Rosbash, M., Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels (1990) Nature, 343, pp. 536-540; Hassfeld, W., Chan, E.K., Mathison, D.A., Portman, D., Dreyfuss, G., Steiner, G., Tan, E.M., Molecular definition of heterogeneous nuclear ribonucleoprotein R (hnRNP R) using autoimmune antibody: Immunological relationship with hnRNP P (1998) Nucleic Acids Res., 26, pp. 439-445; Holcik, M., Korneluk, R.G., Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element: Role of la autoantigen in XIAP translation (2000) Mol. Cell. Biol., 20, pp. 4648-4657; Kim, J.H., Hahm, B., Kim, Y.K., Choi, M., Jang, S.K., Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm (2000) J. Mol. Biol., 298, pp. 395-405; Kim, J.H., Paek, K.Y., Choi, K., Kim, T.-D., Hahm, B., Kim, K.-T., Jang, S.K., Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner (2003) Mol. Cell. Biol., 23, pp. 708-720; Kim, J.H., Paek, K.Y., Ha, S.H., Cho, S., Choi, K., Kim, C.S., Ryu, S.H., Jang, S.K., A cellular RNA-binding protein enhances internal ribosomal entry site-dependent translation through an interaction downstream of the hepatitis C virus polyprotein initiation codon (2004) Mol. Cell. Biol., 24, pp. 7878-7890; Klein, D.C., Weller, J.L., Indole metabolism in the pineal gland: A circadian rhythm in N-acetyltransferase (1970) Science, 169, pp. 1093-1095; Klein, D.C., Ganguly, S., Coon, S.L., Shi, Q., Gaildrat, P., Morin, F., Weller, J.L., Dyda, F., 14-3-3 Proteins in pineal photoneuroendocrine transduction: How many roles? (2003) J. 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year = "2005",
doi = "10.1128/MCB.25.8.3232-3246.2005",
language = "English",
volume = "25",
pages = "3232--3246",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation

AU - Kim, T.-D.

AU - Kim, J.-S.

AU - Jong, H.K.

AU - Myung, J.

AU - Chae, H.-D.

AU - Woo, K.-C.

AU - Sung, K.J.

AU - Koh, D.-S.

AU - Kim, K.-T.

N1 - 引用次數:56 Export Date: 18 September 2018 CODEN: MCEBD 通訊地址: Kim, K.-T.; National Research Laboratory, Department of Life Science, Pohang Univ. of Sci. and Technology, San 31 Hyoja-Dong, Pohang, Kyung-Buk 790-784, South Korea; 電子郵件: ktk@postech.ac.kr 分析序列編號: GENBANK: AF004108, AF092100, AKK59705, AY184814, NM_001533, NM_005817, NM_017008, NM_177509, U29663, U38306, U46502, U46661, XM_008139; 化學物質/CAS: 3' Untranslated Regions; Arylalkylamine N-Acetyltransferase, EC 2.3.1.87; Heterogeneous-Nuclear Ribonucleoproteins; RNA, Messenger; RNA, Small Interfering; RNA-Binding Proteins 參考文獻: Andreason, G.L., Evans, G.A., Introduction and expression of DNA molecules in eukaryotic cells by electroporation (1988) BioTechniques, 6, pp. 650-660; Baler, R., Covington, S., Klein, D.C., The rat arylalkylamine N-acetyltransferase gene promoter: cAMP activation via a cAMP-responsive element-CCAAT complex (1997) J. Biol. Chem., 272, pp. 6979-6985; Bernard, M., Iuvone, P.M., Cassone, V.M., Roseboom, P.H., Coon, S.L., Klein, D.C., Avian melatonin synthesis: Photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina (1997) J. Neurochem., 68, pp. 213-224; Borjigin, J., Wang, M.M., Snyder, S.H., Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal gland (1995) Nature, 378, pp. 783-785; Chae, H.D., Park, T.J., Lee, Y.K., Lee, T.G., Kim, K.T., Rapid and simple measurement of serotonin N-acetyltransferase activity by liquid biphasic diffusion assay (1999) Neurochem. Int., 35, pp. 447-451; Coon, S.L., Roseboom, P.H., Baler, R., Weller, J.L., Namboodiri, M.A., Koonin, E.V., Klein, D.C., Pineal serotonin N-acetyltransferase: Expression cloning and molecular analysis (1995) Science, 270, pp. 1681-1683; Coon, S.L., Del Olmo, E., Young III, W.S., Klein, D.C., Melatonin synthesis enzymes in Macaca mulatta: Focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87) (2002) J. Clin. Endocrinol. Metab., 87, pp. 4699-4706; Craft, C.M., Murage, J., Brown, B., Zhan-Poe, X., Bovine arylalkylamine N-acetyltransferase activity correlated with mRNA expression in pineal and retina (1999) Brain Res. Mol. Brain Res., 65, pp. 44-51; Dreyfuss, G., Kim, V.N., Kataoka, N., Messenger-RNA-binding proteins and the messages they carry (2002) Nat. Rev. Mol. Cell Biol., 3, pp. 195-205; Dunlap, J.C., Molecular bases for circadian clocks (1999) Cell, 96, pp. 271-290; Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., Tuschl, T., Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells (2000) Nature, 411, pp. 494-498; Forger, D.B., Peskin, C.S., A detailed predictive model of the mammalian circadian clock (2003) Proc. Natl. Acad. Sci. USA, 100, pp. 14806-14811; Foulkes, N.S., Borjigin, J., Snyder, S.H., Sassone-Corsi, P., Transcriptional control of circadian hormone synthesis via the CREM feedback loop (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 14140-14145; Foulkes, N.S., Borjigin, J., Snyder, S.H., Sassone-Corsi, P., Rhythmic transcription: The molecular basis of circadian melatonin synthesis (1997) Trends Neurosci., 20, pp. 487-492; Ganguly, S., Coon, S.L., Klein, D.C., Control of melatonin synthesis in the mammalian pineal gland: The critical role of serotonin acetylation (2002) Cell Tissue Res., 309, pp. 127-137; Gastel, J.A., Roseboom, P.H., Rinaldi, P.A., Weller, J.L., Klein, D.C., Melatonin production: Proteasomal proteolysis in serotonin N-acetyltransferase regulation (1998) Science, 279, pp. 1358-1360; Gauer, F., Poierl, V.J., Garidou, M.L., Simonneaux, V., Pevet, P., Molecular cloning of the arylalkylamine N-acetyltransferase and daily variations of its mRNA expression in the Syrian hamster pineal gland (1999) Brain Res. Mol. Brain Res., 71, pp. 87-95; Goldbeter, A., Computational approaches to cellular rhythms (2002) Nature, 420, pp. 238-245; Goodwin, B.C., Oscillatory behavior in enzymatic control processes (1965) Adv. Enzyme Regul., 3, pp. 425-438; Grosset, C., Chen, C.Y., Xu, N., Sonenberg, N., Jacquemin-Sablon, H., Shyu, A.B., A mechanism for translationally coupled mRNA turnover: Interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex (2000) Cell, 103, pp. 29-40; Hahm, B., Cho, O.H., Kim, J.E., Kim, Y.K., Kim, J.H., Oh, Y.L., Jang, S.K., Polypyrimidine tract-binding protein interacts with hnRNP L. (1998) FEBS Lett., 425, pp. 401-406; Hardin, P.E., Hall, J.C., Rosbash, M., Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels (1990) Nature, 343, pp. 536-540; Hassfeld, W., Chan, E.K., Mathison, D.A., Portman, D., Dreyfuss, G., Steiner, G., Tan, E.M., Molecular definition of heterogeneous nuclear ribonucleoprotein R (hnRNP R) using autoimmune antibody: Immunological relationship with hnRNP P (1998) Nucleic Acids Res., 26, pp. 439-445; Holcik, M., Korneluk, R.G., Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element: Role of la autoantigen in XIAP translation (2000) Mol. Cell. Biol., 20, pp. 4648-4657; Kim, J.H., Hahm, B., Kim, Y.K., Choi, M., Jang, S.K., Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm (2000) J. Mol. Biol., 298, pp. 395-405; Kim, J.H., Paek, K.Y., Choi, K., Kim, T.-D., Hahm, B., Kim, K.-T., Jang, S.K., Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner (2003) Mol. Cell. Biol., 23, pp. 708-720; Kim, J.H., Paek, K.Y., Ha, S.H., Cho, S., Choi, K., Kim, C.S., Ryu, S.H., Jang, S.K., A cellular RNA-binding protein enhances internal ribosomal entry site-dependent translation through an interaction downstream of the hepatitis C virus polyprotein initiation codon (2004) Mol. Cell. Biol., 24, pp. 7878-7890; Klein, D.C., Weller, J.L., Indole metabolism in the pineal gland: A circadian rhythm in N-acetyltransferase (1970) Science, 169, pp. 1093-1095; Klein, D.C., Ganguly, S., Coon, S.L., Shi, Q., Gaildrat, P., Morin, F., Weller, J.L., Dyda, F., 14-3-3 Proteins in pineal photoneuroendocrine transduction: How many roles? (2003) J. Neuroendocrinol., 15, pp. 370-377; Lee, C., Etchegaray, J.P., Cagampang, F.R.A., London, A.S.I., Reppert, S.M., Posttranslational mechanisms regulate the mammalian circadian clock (2001) Cell, 107, pp. 855-867; Leloup, J.C., Goldbeter, A., Toward a detailed computational model for the mammalian circadian clock (2003) Proc. Natl. Acad. Sci. USA, 100, pp. 7051-7056; Lowrey, P.L., Shimomura, K., Antoch, M.P., Yamazaki, S., Zemenides, P.D., Ralph, M.R., Menaker, M., Takahashi, J.S., Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau (2000) Science, 288, pp. 483-492; Mayr, B., Montminy, M., Transcriptional regulation by the phosphorylation-dependent factor CREB (2001) Nat. Rev. Mol. Cell Biol., 2, pp. 599-609; McAdams, H.H., Arkin, A., Simulation of prokaryotic genetic circuits (1998) Annu. Rev. Biophys. Biomol. Struct., 27, pp. 199-224; Mitchell, P., Tollervey, D., mRNA stability in eukaryotes (2000) Curr. Opin. Genet. 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PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - cis acting element

KW - heterogeneous nuclear ribonucleoprotein

KW - heterogeneous nuclear ribonucleoprotein L

KW - heterogeneous nuclear ribonucleoprotein Q

KW - heterogeneous nuclear ribonucleoprotein R

KW - messenger RNA

KW - serotonin n acetyltransferase

KW - unclassified drug

KW - 3' untranslated region

KW - animal cell

KW - animal experiment

KW - animal tissue

KW - article

KW - circadian rhythm

KW - controlled study

KW - gene overexpression

KW - mathematical model

KW - nonhuman

KW - nucleotide sequence

KW - oscillation

KW - pineal body

KW - pinealocyte

KW - priority journal

KW - protein analysis

KW - rat

KW - RNA degradation

KW - RNA interference

KW - RNA stability

KW - species difference

KW - 3' Untranslated Regions

KW - Animals

KW - Arylalkylamine N-Acetyltransferase

KW - Base Sequence

KW - Circadian Rhythm

KW - Heterogeneous-Nuclear Ribonucleoproteins

KW - Molecular Sequence Data

KW - Pineal Gland

KW - Rats

KW - RNA Stability

KW - RNA, Messenger

KW - RNA, Small Interfering

KW - RNA-Binding Proteins

U2 - 10.1128/MCB.25.8.3232-3246.2005

DO - 10.1128/MCB.25.8.3232-3246.2005

M3 - Article

VL - 25

SP - 3232

EP - 3246

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 8

ER -