title: The 3'-untranslated regions of c-mos and cyclin mRNAs stimulate translation by regulating cytoplasmic polyadenylation.
abstract: Early in the development of many animals, before transcription begins, any change in the pattern of protein synthesis is attributable to a change in the translational activity or stability of an mRNA in the egg. As a result, translational control is critical for a variety of developmental decisions, including axis formation in Drosophila and sex determination in Caenorhabditis elegans. Previous work demonstrated that increases in poly(A) length can activate translation, whereas removal of poly(A) can prevent it. In this report we focus on the control of c-mos and cyclin A1, B1, and B2 mRNAs during meiotic maturation and after fertilization of frog eggs. We show that addition and removal of poly(A) from these mRNAs is extensively regulated: The time at which each mRNA receives or loses poly(A), as well as the number of adenosines it gains or loses, differ substantially. Signals in the 3'-untranslated region (UTR) of each mRNA are sufficient to reconstitute both the temporal and quantitative control of poly(A) addition: Chimeric mRNAs in which a luciferase-coding region is joined to the 3' UTRs of cyclin A1, cyclin B1, or c-mos mRNA, receive poly(A) of the same length and at the same time as do the endogenous mRNAs. Moreover, each 3' UTR also regulates translation of the chimeric mRNAs, determining when and how much translation of the luciferase reporter is stimulated during maturation. The magnitude of stimulation in luciferase activity varies from 5- to 100-fold, depending on the 3' UTR. Translational stimulation by each 3' UTR requires poly(A) lengthening, as it is prevented by mutations that prevent that process. These results suggest that the 3' UTRs of cyclin and c-mos mRNAs control not only whether or not an mRNA is turned on during maturation, but when that activation occurs and to what extent. Translational control of c-mos mRNA, which may be achieved through regulation of poly(A) length, may be critical in the activation of maturation, and in the onset of cleavage divisions. Our findings, as well as those of others, suggest that even quite complex patterns of translational activation in the early embryo can be attained through the differential control of a common mechanism.
authors.affiliation: Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison 53706.
authors.forename: M D
authors.initials: MD
authors.lastname: Sheets
authors.forename: C A
authors.initials: CA
authors.lastname: Fox
authors.forename: T
authors.initials: T
authors.lastname: Hunt
authors.forename: G
authors.initials: G
authors.lastname: Vande Woude
authors.forename: M
authors.initials: M
authors.lastname: Wickens
mesh_terms: D000818:Animals; D001483:Base Sequence; D019925:Cyclin A; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D005306:Fertilization / Q000502:physiology; D008540:Meiosis / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D017231:Proto-Oncogene Proteins c-mos / Q000096:biosynthesis* / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D019925:Cyclin A; D016213:Cyclins; D012333:RNA, Messenger; D029867:Xenopus Proteins; C516049:cyclin A1, Xenopus; D011374:Progesterone; D017231:Proto-Oncogene Proteins c-mos