Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complex molecular systems involved in the process of sex-differentiation and fertility in Schistosoma mansoni have not yet been completely described. Using a 4608-element cDNA microarray, we have now determined 90 and 139 genes with significantly (q-value</=0.06) higher expression levels in adult males and females, respectively. Eight out of eleven (73%) selected transcripts had their differential expression levels validated by real-time RT-PCR. One of these transcripts was extended by RT-PCR and was shown to span the intronic region between exons 9 and 11 of the S. mansoni CA150 gene, a transcriptional cofactor known in humans to interact with both RNA polymerase II and the spliceosome complex. The longer transcript probably represents a novel isoform of S. mansoni CA150. Additionally, we obtained full-length sequences for three other isoforms of the SmCA150 gene, coding for proteins of different lengths and domain compositions. Semi-quantitative RT-PCR showed different expression ratios among these isoforms between male and female. Due to the role of CA150 in RNA transcription and processing, we hypothesize that these differential expression events may be important in the generation and maintenance of the different phenotypes between male and female.
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PMID:Gender biased differential alternative splicing patterns of the transcriptional cofactor CA150 gene in Schistosoma mansoni. 1690

We present a novel structure determination approach that exploits the global orientational restraints from RDCs to resolve ambiguous NOE assignments. Unlike traditional approaches that bootstrap the initial fold from ambiguous NOE assignments, we start by using RDCs to compute accurate secondary structure element (SSE) backbones at the beginning of structure calculation. Our structure determination package, called RDC-PANDA: (RDC-based SSE PAcking with NOEs for Structure Determination and NOE Assignment), consists of three modules: (1) RDC-EXACT: ; (2) PACKER: ; and (3) HANA: (HAusdorff-based NOE Assignment). RDC-EXACT: computes the global optimal solution of backbone dihedral angles for each secondary structure element by exactly solving a system of quartic RDC equations derived by Wang and Donald (Proceedings of the IEEE computational systems bioinformatics conference (CSB), Stanford, CA, 2004a; J Biomol NMR 29(3):223-242, 2004b), and systematically searching over the roots, each of which is a backbone dihedral varphi- or psi-angle consistent with the RDC data. Using a small number of unambiguous inter-SSE NOEs extracted using only chemical shift information, PACKER: performs a systematic search for the core structure, including all SSE backbone conformations. HANA: uses a Hausdorff-based scoring function to measure the similarity between the experimental spectra and the back-computed NOE pattern for each side-chain from a statistically-diverse rotamer library, and drives the selection of optimal position-specific rotamers for filtering ambiguous NOE assignments. Finally, a local minimization approach is used to compute the loops and refine side-chain conformations by fixing the core structure as a rigid body while allowing movement of loops and side-chains. RDC-PANDA: was applied to NMR data for the FF Domain 2 of human transcription elongation factor CA150 (RNA polymerase II C-terminal domain interacting protein), human ubiquitin, the ubiquitin-binding zinc finger domain of the human Y-family DNA polymerase Eta (pol eta UBZ), and the human Set2-Rpb1 interacting domain (hSRI). These results demonstrated the efficiency and accuracy of our algorithm, and show that RDC-PANDA: can be successfully applied for high-resolution protein structure determination using only a limited set of NMR data by first computing RDC-defined backbones.
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PMID:High-resolution protein structure determination starting with a global fold calculated from exact solutions to the RDC equations. 1971 Nov 85

FF domains are poorly understood protein interaction modules that are present within eukaryotic transcription factors, such as CA150 (TCERG-1). The CA150 FF domains have been shown to mediate interactions with the phosphorylated C-terminal domain of RNA polymerase II (phosphoCTD) and a multitude of transcription factors and RNA processing proteins, and may therefore have a central role in organizing transcription. FF domains occur in tandem arrays of up to six domains, although it is not known whether they adopt higher-order structures. We have used the CA150 FF1+FF2 domains as a model system to examine whether tandem FF domains form higher-order structures in solution using NMR spectroscopy. In the solution structure of FF1 fused to the linker that joins FF1 to FF2, we observed that the highly conserved linker peptide is ordered and forms a helical extension of helix alpha3, suggesting that the interdomain linker might have a role in orientating FF1 relative to FF2. However, examination of the FF1+FF2 domains using relaxation NMR experiments revealed that although these domains are not rigidly orientated relative to one another, they do not tumble independently. Thus, the FF1+FF2 structure conforms to a dumbbell-shape in solution, where the helical interdomain linker maintains distance between the two dynamic FF domains without cementing their relative orientations. This model for FF domain organization within tandem arrays suggests a general mechanism by which individual FF domains can manoeuvre to achieve optimal recognition of flexible binding partners, such as the intrinsically-disordered phosphoCTD.
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PMID:Structural studies of FF domains of the transcription factor CA150 provide insights into the organization of FF domain tandem arrays. 1971 1

Because of their sessile nature, plants have adopted varied strategies for growing and reproducing in an ever-changing environment. Control of mRNA levels and pre-mRNA alternative splicing are key regulatory layers that contribute to adjust and synchronize plant growth and development with environmental changes. Transcription and alternative splicing are thought to be tightly linked and coordinated, at least in part, through a network of transcriptional and splicing regulatory factors that interact with the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II. One of the proteins that has been shown to play such a role in yeast and mammals is pre-mRNA-PROCESSING PROTEIN 40 (PRP40, also known as CA150, or TCERG1). In plants, members of the PRP40 family have been identified and shown to interact with the CTD of RNA Pol II, but their biological functions remain unknown. Here, we studied the role of AtPRP40C, in Arabidopsis thaliana growth, development and stress tolerance, as well as its impact on the global regulation of gene expression programs. We found that the prp40c knockout mutants display a late-flowering phenotype under long day conditions, associated with minor alterations in red light signaling. An RNA-seq based transcriptome analysis revealed differentially expressed genes related to biotic stress responses and also differentially expressed as well as differentially spliced genes associated with abiotic stress responses. Indeed, the characterization of stress responses in prp40c mutants revealed an increased sensitivity to salt stress and an enhanced tolerance to Pseudomonas syringae pv. maculicola (Psm) infections. This constitutes the most thorough analysis of the transcriptome of a prp40 mutant in any organism, as well as the first characterization of the molecular and physiological roles of a member of the PRP40 protein family in plants. Our results suggest that PRP40C is an important factor linking the regulation of gene expression programs to the modulation of plant growth, development, and stress responses.
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PMID:A Role for Pre-mRNA-PROCESSING PROTEIN 40C in the Control of Growth, Development, and Stress Tolerance in Arabidopsis thaliana. 3145 14


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