title: Non-equivalent Roles of AGO1 and AGO2 in mRNA Turnover and Translation of Cyclin D1 mRNA.
abstract: Mammalian Argonaute proteins (AGO1-4), in combination with microRNAs (miRs), bind to target mRNAs to initiate degradation and/or translation repression, but the relationships between these two effects is unclear. Although the AGO isoforms ofDrosophilaand plants perform different functions, mammalian AGO isoforms are considered to be functionally degenerate in terms of miR loading and downstream silencing effects. However, we found that, in quiescent (G0) rat myoblasts transiting to the G1 phase, cyclin D1 (Ccnd1) mRNA was associated with two functionally distinct AGO-miR complexes. While AGO1-miR-1 down-regulated the mRNA level, AGO2-let-7 delayed the timing of translation. Knockdown (KD) of AGO2, or antisense-mediated depletion of Let-7, caused Ccnd1 translation to occur earlier, but had no significant effect on mRNA abundance. Conversely, down-regulation of either AGO1 or miR-1, resulted in elevated Ccnd1 mRNA levels at early times, but failed to affect the timing of translation. These results show that the two miR-mediated silencing effects, viz. mRNA decay and translation repression, are independent processes induced by individual AGO isoforms in association with specific miRs.
authors: From the Genetic Engineering Laboratory, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700032, India.
authors: Utpalendu
authors: U
authors: Ghosh
authors: From the Genetic Engineering Laboratory, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700032, India nilugrandson@gmail.com.
authors: Samit
authors: S
authors: Adhya
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: C582332:Ago2 protein, rat; D060565:Argonaute Proteins; C530106:Ccnd1 protein, rat; C542191:MIRN1 microRNA, rat; C556274:MIRN26 microRNA, rat; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1
keywords: Argonaute; cyclin D1; mRNA; microRNA (miRNA); myogenesis