Project description:The noncoding genome plays an important role in de novo gene birth and the emergence of genetic novelty. Nevertheless, how the properties of noncoding sequences could promote the birth of novel genes and shape the structural diversity and evolution of proteins remains unclear. Here, we investigated the potential of the noncoding genome of yeast to produce novel protein bricks that can give rise to novel genes or be integrated in pre-existing proteins, thus participating in protein structure evolution and diversity. Combining different bioinformatics approaches, we showed that intergenic ORFs of yeast encompass the large structural diversity of canonical proteins with the majority encoding peptides predicted as foldable. Then, we investigated the early stages of de novo gene birth with Ribosome Profiling and systematic reconstruction of yeast de novo gene ancestral sequences. We highlighted sequence and structural factors determining de novo gene birth and protein evolution. Finally, we showed a strong correlation between the fold potential of de novo genes and their ancestral ORFs reflecting the relationship between the noncoding genome and the protein structure universe.
Project description:This data set represents the results of two reverse labeled experiments from wild-type and RRP6delta S. cerevisiae that has been hybed to arrays containing PCR products for ORFs and Intergenic Features Keywords: genetic modification
Project description:We used a microarray covering the whole genome of R. conorii to check if intergenic sequences were found transcribed. We checked the expression signals for probes corresponding to spacers as compared to probes corresponding to Open Reading Frames (ORFs). We got total RNA from R. conorii XTC cultures; we performed cDNA synthesis and then hybridizations. The hybridizations were repeated four times, and data were compared to check the reproducibility.
Project description:We conducted a genome-wide placental transcriptome study aiming at the identification of functional pathways representing the molecular link between maternal pre-pregnancy BMI and fetal growth. We used RNA microarray (Agilent 8 X 60 K), medical records, and questionnaire data from 183 mother-newborn pairs from the ENVIRONAGE birth cohort study (Flanders, Belgium). We applied a weighted gene co-expression network analysis (WGCNA) and identified genes modules and hub genes that were associated with maternal BMI as well as newborn birth weight. Modules of interest were further characterized by gene ontology (GO) and pathway enrichment analyses. We assessed the mediating effects of modules and hub genes in the association between maternal BMI and newborn weight.
Project description:Preterm birth, defined as birth <37 weeks of gestation, is a leading cause of infant morbidity and mortality. In the United States, approximately 12% of all births are preterm.1 Despite decades of research, there has been little progress in developing effective interventions to prevent preterm birth. In fact, the rate of preterm birth has increased slightly over the last several decades.2 The ultimate goal of the Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) is to identify possible biomarkers that could predict the susceptibility to spontaneous preterm birth (SPTB) as well as to shed light on the molecular mechanisms involved in its etiologies. Understanding those mechanisms will help us predict SPTB and may facilitate the introduction of more effective prevention and treatment strategies.
Project description:Contains a row for each intergenic region in each sample, indicating whether our analysis called a window within the region "present" or "absent" in the sample. Intergenic regions are regions containing neither annotated genes nor intergenic clusters. Region coordinates refer to version 3 of the TIGR annotation as submitted to GenBank (GI numbers 22330780, 22326553, 22331929, 22329272, 22328163). Keywords: other
Project description:Contains a row for each intergenic region in each sample, indicating whether our analysis called a window within the region "present" or "absent" in the sample. Intergenic regions are regions containing neither annotated genes nor intergenic clusters. Region coordinates refer to version 3 of the TIGR annotation as submitted to GenBank (GI numbers 22330780, 22326553, 22331929, 22329272, 22328163).
Project description:There is increasing evidence that the architecture of long non-coding RNAs – just like that of proteins – is hierarchically organized into independently folding sub-modules with distinct functions. Studies characterizing the cellular activities of such modules, however, are rare. The lncRNA growth arrest specific 5 (Gas5) is a key regulator of cell survival in response to stress and nutrient availability. We used SHAPE-MaP to probe the structure of Gas5 in vitro and in cellulo. The results show that Gas5 contains three separate structural modules including the previously predicted steroid receptor binding hairpin motif. Functional assays show that the newly identified modules act independently in leukemic T cells. The 5’ terminal module with low secondary structure content affects basal survival and slows the cell cycle, whereas the highly structured core module mediates the effects of mTOR inhibition on cell growth. Disruption of specific secondary structures within the modules abolish their function in cells. These results highlight the central role of Gas5 in regulating cell survival and reveals how a single lncRNA transcript utilizes a modular structure-function relationship to respond to a variety of cellular stresses under various cellular conditions.
Project description:Brr2 is a DExD/H-box helicase responsible for U4/U6 unwinding, a critical step in spliceosomal activation. Brr2 contains an N-terminal domain and two tandem sets of a helicase-like domain followed by a Sec63 domain with unknown function. We determined the crystal structure of the second Sec63 domain, which unexpectedly resembles domains 4 and 5 of DNA helicase Hel308. The helicase-like domain upstream of Sec63 has clear sequence similarity with domains 1-3 of Hel308. In addition modeling indicates that Brr2 is composed of an N-terminal domain and two consecutive Hel308-like modules (Hel308-I and II). Together this provides our first glimpse of the overall structure of this large and unique spliceosomal ATPase and helicase. Our structural model and mutagenesis data suggest that Brr2 shares a similar helicase mechanism to Hel308, that differs from many DEAD-box proteins. We demonstrate that Hel308-II interacts with Prp8 and Snu114 in vitro and in vivo, potentially serving as a mediator for the regulation of Brr2â??s activity by Prp8. We further find that the C-terminal region of Prp8 (Prp8-CTR) facilitates the binding of the Brr2/Prp8-CTR complex to U4/U6, suggesting a potential role of Prp8-CTR as an auxiliary substrate binding and specificity domain for Brr2. Splicing specific microarrays were used to assess the genome-wide defects in pre-mRNA splicing that result from a deletion of the second Sec63 domain of yeast Brr2.
Project description:Contains a row for each intergenic cluster in each sample, indicating whether our analysis called the cluster "present" or "absent" in the sample. Intergenic clusters are novel (unannotated) genes detected by aligning Arabidopsis cDNAs/ESTs to the genome. Cluster coordinates refer to version 3 of the TIGR annotation as submitted to GenBank (GI numbers 22330780, 22326553, 22331929, 22329272, 22328163). Keywords: other