The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation. The first-AUG rule is not absolute, but there are rules for breaking the rule. Some anomalous observations that seemed to contradict the scanning mechanism now appear to be artifacts. A few genuine anomalies remain unexplained.

/pdf/the-scanning-model-for-translation-an-update-52r2in8l71.pdf

The scanning model for translation: an update.

In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure. When protein folding in the ER is inhibited, signal transduction pathways, which increase the biosynthetic capacity and decrease the biosynthetic burden of the ER to maintain the homeostasis of this organelle, are activated. These pathways are called the unfolded protein response (UPR). In this review, we briefly summarize principles of protein folding and molecular chaperone function important for a mechanistic understanding of UPR-signaling events. We then discuss mechanisms of signal transduction employed by the UPR in mammals and our current understanding of the remodeling of cellular processes by the UPR. Finally, we summarize data that demonstrate that UPR signaling feeds into decision making in other processes previously thought to be unrelated to ER function, e.g., eukaryotic starvation responses and differentiation programs.

The mammalian unfolded protein response

The identification of untranslated regions, introns, and coding regions within an organism remains challenging. We developed a quantitative sequencing-based method called RNA-Seq for mapping transcribed regions, in which complementary DNA fragments are subjected to high-throughput sequencing and mapped to the genome. We applied RNA-Seq to generate a high-resolution transcriptome map of the yeast genome and demonstrated that most (74.5%) of the nonrepetitive sequence of the yeast genome is transcribed. We confirmed many known and predicted introns and demonstrated that others are not actively used. Alternative initiation codons and upstream open reading frames also were identified for many yeast genes. We also found unexpected 3'-end heterogeneity and the presence of many overlapping genes. These results indicate that the yeast transcriptome is more complex than previously appreciated.

/pdf/the-transcriptional-landscape-of-the-yeast-genome-defined-by-p354u8wkq4.pdf

The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing

Diploid cells of budding yeast produce haploid cells through the developmental program of sporulation, which consists of meiosis and spore morphogenesis DNA microarrays containing nearly every yeast gene were used to assay changes in gene expression during sporulation At least seven distinct temporal patterns of induction were observed The transcription factor Ndt80 appeared to be important for induction of a large group of genes at the end of meiotic prophase Consensus sequences known or proposed to be responsible for temporal regulation could be identified solely from analysis of sequences of coordinately expressed genes The temporal expression pattern provided clues to potential functions of hundreds of previously uncharacterized genes, some of which have vertebrate homologs that may function during gametogenesis

/pdf/the-transcriptional-program-of-sporulation-in-budding-yeast-4oqyqqmn64.pdf

The Transcriptional Program of Sporulation in Budding Yeast

http://wolfson.huji.ac.il/expression/local/kozak.pdf

Structural features in eukaryotic mRNAs that modulate the initiation of translation.

Role of MADS box proteins and their cofactors in combinatorial control of gene expression and cell development

The leader peptide of yeast gene CPA1 is essential for the translational repression of its expression

Laboratoire de Microbiologic Universite Libre de Bruxelles tlnstitut de Recherches du CERIA Avenue Emile Gryson 1 B-1070 Brussels, Belgium Summary The expression of gene CPM, encoding the glutamin- ase subunit of the arginine pathway carbamoyl-phos- phate synthetase, is repressed by arginine at a post- transcriptional level. The 5’ region of CPAf mRNA contains a 25 codon upstream open reading frame. The importance of this feature for the repression of CPA7 expression has been analyzed by oligonucleo- tide-directed mutagenesis and by sequencing of con- stitutive &-dominant mutations obtained in vivo. The results show that the leader peptide, the product of the upstream open reading frame, plays an essential, negative role in the specific repression of CPA7 by ar- ginine. A model of translational regulation of CPA7 is proposed that takes into account the cis-dominance of the mutations affecting the leader peptide. Introduction In Saccharomyces cerevisiae two types of control mecha- nism modulate enzyme synthesis in amino acid biosyn- thetic pathways. Many pathways are subject to the general control of amino acid biosynthesis and are derepressed in response to starvation for any of a number of amino acids (reviewed in Jones and Fink, 1982). The general control operates at the level of transcription and is superimposed on specific control mechanisms whereby the end product represses the synthesis of the enzymes that specifically lead to its own synthesis (reviewed in Jones and Fink, 1982). This is the case for the arginine pathway and its carbamoyl-phosphate synthetase (CPSase) (reviewed by Davis, 1986). Two independently regulated CPSases produce car- bamoyl phosphate for the pyrimidine and arginine biosyn- theses in yeast (Lacroute et al., 1965). One synthetase, CPSase P is repressed and feedback-inhibited by the pyrimidines, whereas another synthetase, CPSase A, is repressed by arginine. CPSase A comprises two noniden- tical subunits, encoded by the unlinked genes

https://www.cell.com/cell/pdf/0092-8674(87)90618-0.pdf

The Leader Peptide of Yeast Gene CPA7 Is Essential for the Translational Repression of Its Expression

This report describes the identification, cloning, and molecular analysis of UME6 (CAR80/CARGRI), a key transcriptional regulator of early meiotic gene expression. Loss of UME6 function results in the accumulation of fully derepressed levels (70- to 100-fold increase above basal level) of early meiotic transcripts during vegetative growth. In contrast, mutations in five previously identified UME loci (UME1 to UME5), result in low to moderate derepression (2- to 10-fold increase) of early meiotic genes. The behavior of insertion and deletion alleles indicates that UME6 is dispensable for mitotic division but is required for meiosis and spore germination. Despite the high level of meiotic gene expression during vegetative growth, the generation times of ume6 mutant haploid and diploid cells are only slightly reduced. However, both ascus formation and spore viability are affected more severely. The UME6 gene encodes a 91-kD protein that contains a C6 zinc cluster motif similar to the DNA-binding domain of GAL4. The integrity of this domain is required for UME6 function. It has been reported recently that a mutation in CAR80 fails to complement an insertion allele of UME6. CAR80 is a gene required for nitrogen repression of the arginine catabolic enzymes. Here, through sequence analysis, we demonstrate that UME6 and CAR80 are identical. Analyses of UME6 mRNA during both nitrogen starvation and meiotic development indicate that its transcription is constitutive, suggesting that regulation of UME6 activity occurs at a post-transcriptional level.

/pdf/ume6-is-a-key-regulator-of-nitrogen-repression-and-meiotic-48tk8bcx86.pdf

UME6 is a key regulator of nitrogen repression and meiotic development.

The regulation of arginine biosynthetic enzymes in yeast is subjected to a double control. One level of arginine enzyme synthesis is under the control of an apo-repressor, called ARGR. ARGR molecules control specifically the arginine pathway.



A second level of control of arginine biosynthesis has been disclosed. It also controls tryptophan, histidine, lysine, isoleucine-valine and leucine, and probably many more biosyntheses. The general mechanism is turned on in leaky mutants in any of the amino acid pathways mentioned above.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1975.tb02295.x

The regulation of arginine biosynthesis in Saccharomyces cerevisiae. The specificity of argR- mutations and the general control of amino-acid biosynthesis.

Francine Messenguy

Papers

Role of MADS box proteins and their cofactors in combinatorial control of gene expression and cell development

The leader peptide of yeast gene CPA1 is essential for the translational repression of its expression

The Leader Peptide of Yeast Gene CPA7 Is Essential for the Translational Repression of Its Expression

UME6 is a key regulator of nitrogen repression and meiotic development.

The regulation of arginine biosynthesis in Saccharomyces cerevisiae. The specificity of argR- mutations and the general control of amino-acid biosynthesis.