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An integrative genomics approach to infer causal associations between gene expression and disease
It is shown that this approach can predict transcriptional responses to single gene–perturbation experiments using gene-expression data in the context of a segregating mouse population and the utility of this approach is demonstrated by identifying and experimentally validating the involvement of three new genes in susceptibility to obesity. Expand
Circularization of mRNA by eukaryotic translation initiation factors.
The reconstitution of an eIF4E/eIF4G/Pab1p complex with recombinant proteins is demonstrated and it is shown that the complex can circularize capped, polyadenylated RNA, suggesting that formation of circular mRNA by translation factors could contribute to the control of mRNA expression in the eukaryotic cell. Expand
Glucose depletion rapidly inhibits translation initiation in yeast.
It is discovered that glucose withdrawal from the growth medium led to a rapid inhibition of protein synthesis and that this effect was readily reversed upon readdition of glucose, highlighting the intimate connection between the nutrient status of the cell and its translational capacity. Expand
Ribosome Loading onto the mRNA Cap Is Driven by Conformational Coupling between eIF4G and eIF4E
The data explain how mRNA, eif4E, and eIF4G exists as a stable mRNP that may facilitate multiple rounds of ribosomal loading during translation initiation, a key determinant in the overall rate of protein synthesis. Expand
The poly(A) binding protein is required for poly(A) shortening and 60S ribosomal subunit-dependent translation initiation
Data suggest that the 60S subunit mediates the PAB requirement of translation initiation, thereby ensuring that only intact poly(A)+ mRNA will be translated efficiently in vivo. Expand
Genetic inheritance of gene expression in human cell lines.
- S. Monks, A. Leonardson, +6 authors E. Schadt
- Biology, Medicine
- American journal of human genetics
- 1 December 2004
This work presents the largest survey to date, to the authors' knowledge, of the heritability of gene-expression traits in segregating human populations, and views clusters or networks based on genetic correlation measures and shared QTLs as potentially novel insights into the relationship among genes that may underlie complex traits. Expand
Association of the yeast poly(A) tail binding protein with translation initiation factor eIF‐4G.
Although the cap structure and the poly(A) tail are on opposite ends of the mRNA molecule, previous work has suggested that they interact to enhance translation and inhibit mRNA degradation. Here we… Expand
Poly(A) Tail Length Control in Saccharomyces cerevisiae Occurs by Message-Specific Deadenylation
- Christine E. Brown, A. Sachs
- Medicine, Biology
- Molecular and Cellular Biology
- 1 November 1998
Evidence is provided for an initial phase of mRNA deadenylation that is required for poly(A) tail length control in vivo, and a model whereby mRNAs are polyadenylated by the 3′-end processing machinery with a long tail, possibly of default length, and then in a PAN-dependent manner, the poly (A) tails are rapidly matured to a message-specific length is supported. Expand
A single domain of yeast poly(A)-binding protein is necessary and sufficient for RNA binding and cell viability.
The poly(A)-binding protein (PAB) gene of Saccharomyces cerevisiae is essential for cell growth and neither an octapeptide sequence conserved among eucaryotic RNA-binding proteins nor the C-terminal domain of PAB is required for function in vivo. Expand
A single gene from yeast for both nuclear and cytoplasmic polyadenylate-binding proteins: Domain structure and expression
DNA sequence determination reveals four tandemly arrayed 90 amino acid regions of homology that probably represent poly(A)-binding domains in Saccharomyces cerevisiae, raising the possibility of feedback regulation of translation. Expand