title: MicroRNA-185 oscillation controls circadian amplitude of mouse Cryptochrome 1 via translational regulation.
abstract: Mammalian circadian rhythm is observed not only at the suprachiasmatic nucleus, a master pacemaker, but also throughout the peripheral tissues. Investigation of the regulation of clock gene expression has mainly focused on transcriptional and posttranslational modifications, and little is known about the posttranscriptional regulation of these genes. In the present study, we investigate the role of microRNAs (miRNAs) in the posttranscriptional regulation of the 3'-untranslated region (UTR) of the mouse Cryptochrome 1 (mCry1) gene. Knockdown of Drosha, Dicer, or Argonaute2 increased mCry1-3'UTR reporter activity. The presence of the miRNA recognition element of mCry1 that is important for miR-185 binding decreased mCRY1 protein, but not mRNA, level. Cytoplasmic miR-185 levels were nearly antiphase to mCRY1 protein levels. Furthermore, miR-185 knockdown elevated the amplitude of mCRY1 protein oscillation. Our results suggest that miR-185 plays a role in the fine-tuned regulation of mCRY1 protein expression by controlling the rhythmicity of mCry1 mRNA translation.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Republic of Korea.
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Lee
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Hwa-Rim
authors.initials: HR
authors.lastname: Lee
authors.forename: Wanil
authors.initials: W
authors.lastname: Kim
authors.forename: Do-Yeon
authors.initials: DY
authors.lastname: Kim
authors.forename: Jae-Cheon
authors.initials: JC
authors.lastname: Shin
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Yoo
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; C538964:Cry1 protein, mouse; D056931:Cryptochromes; D035683:MicroRNAs; C578934:Mirn185 microRNA, mouse; D034741:RNA, Small Interfering; C509781:Dicer1 protein, mouse; C513400:Drosha protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases