title: Positive and negative cis-regulatory elements directing postfertilization maternal mRNA translational control in mouse embryos.
abstract: Mechanisms providing for temporally complex patterns of maternal mRNA translation after fertilization are poorly understood. We employed bioinformatics analysis to compare populations of mRNAs enriched specifically on polysomes at the metaphase II (MII) stage oocyte and late one-cell stages and a detailed deletion/truncation series to identify elements that regulate translation. We used the Bag4 3' untranslated region (UTR) as a model. Bioinformatics analysis revealed one conserved motif, subsequently confirmed by functional studies to be a key translation repressor element. The deletion/truncation studies revealed additional regulatory motifs, most notably a strong translation activator element of <30 nt. Analysis of mRNA secondary structure suggests that secondary structure plays a key role in translation repression. Additional bioinformatics analysis of the regulated mRNA population revealed a diverse collection of regulatory motifs found in small numbers of mRNAs, highlighting a high degree of sequence diversity and combinatorial complexity in the overall control of the maternal mRNA population. We conclude that translational control after fertilization is driven primarily by negative regulatory mechanisms opposing strong translational activators, with stage-specific release of the inhibitory influences to permit recruitment. The combination of bioinformatics analysis and deletion/truncation studies provides the necessary approach for dissecting postfertilization translation regulatory mechanisms.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Information Science and Technology Center, Temple University, Philadelphia, PA 19140, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Potireddy
authors.forename: Uros
authors.initials: U
authors.lastname: Midic
authors.forename: Cheng-Guang
authors.initials: CG
authors.lastname: Liang
authors.forename: Zoran
authors.initials: Z
authors.lastname: Obradovic
authors.forename: Keith E
authors.initials: KE
authors.lastname: Latham
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019295:Computational Biology; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D023121:RNA, Messenger, Stored / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C487979:Bag4 protein, mouse; D023121:RNA, Messenger, Stored