1. Detecting allosteric sites of HIV-1 reverse transcriptase by X-ray crystallographic fragment screening.

    Journal of medicinal and pharmaceutical chemistry 56(7):2738 (2013) PMID 23342998 PMCID PMC3906421

    HIV-1 reverse transcriptase (RT) undergoes a series of conformational changes during viral replication and is a central target for antiretroviral therapy. The intrinsic flexibility of RT can provide novel allosteric sites for inhibition. Crystals of RT that diffract X-rays to better than 2 Å res...
  2. Structure of the guanylyltransferase domain of human mRNA capping enzyme.

    PNAS 108(25):10104 (2011) PMID 21636784 PMCID PMC3121809

    The enzyme guanylyltransferase (GTase) plays a central role in the three-step catalytic process of adding an (m7)GpppN cap cotranscriptionally to nascent mRNA (pre-mRNAs). The 5'-mRNA capping process is functionally and evolutionarily conserved from unicellular organisms to human. However, the G...
  3. Cap and cap-binding proteins in the control of gene expression.

    WIREs RNA 2(2):277 (2011) PMID 21957010

    The 5' mRNA cap structure is essential for efficient gene expression from yeast to human. It plays a critical role in all aspects of the life cycle of an mRNA molecule. Capping occurs co-transcriptionally on the nascent pre-mRNA as it emerges from the RNA exit channel of RNA polymerase II. The c...
  4. Species-specific cis-regulatory elements in the 3'-untranslated region direct alternative polyadenylation of bone morphogenetic protein 2 mRNA.

    Journal of Biological Chemistry 283(42):28010 (2008) PMID 18703506 PMCID PMC2661379

    BMP2 (bone morphogenetic protein 2) is a multifunctional member of the transforming growth factor-beta family of growth factors. Disruption of BMP2 signaling results in developmental defects, cancers, and other diseases. BMP2 mRNAs are alternatively polyadenylated, resulting in mRNAs with distin...
  5. Apoptosis and autophagy induction in mammalian cells by small interfering RNA knockdown of mRNA capping enzymes.

    Molecular and Cellular Biology 28(19):5829 (2008) PMID 18678651 PMCID PMC2547012

    Addition of a 5' cap to RNA polymerase II transcripts, the first step of pre-mRNA processing in eukaryotes from yeasts to mammals, is catalyzed by the sequential action of RNA triphosphatase, guanylyltransferase, and (guanine-N-7)methyltransferase. The effects of knockdown of these capping enzym...
  6. Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design.

    Nucleic Acids Research 36(15):5083 (2008) PMID 18676450 PMCID PMC2528191

    HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at approximately 2.5-3.0 A resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitor...
  7. High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations.

    PNAS 105(5):1466 (2008) PMID 18230722 PMCID PMC2234167

    TMC278 is a diarylpyrimidine (DAPY) nonnucleoside reverse transcriptase inhibitor (NNRTI) that is highly effective in treating wild-type and drug-resistant HIV-1 infections in clinical trials at relatively low doses ( approximately 25-75 mg/day). We have determined the structure of wild-type HIV...
  8. Human capping enzyme promotes formation of transcriptional R loops in vitro.

    PNAS 104(45):17620 (2007) PMID 17978174 PMCID PMC2077024

    Cap formation is the first step of pre-mRNA processing in eukaryotic cells. Immediately after transcription initiation, capping enzyme (CE) is recruited to RNA polymerase II (Pol II) by the phosphorylated carboxyl-terminal domain of the Pol II largest subunit (CTD), allowing cotranscriptional ca...
  9. Human mRNA cap methyltransferase: alternative nuclear localization signal motifs ensure nuclear localization required for viability.

    Molecular and Cellular Biology 25(7):2644 (2005) PMID 15767670 PMCID PMC1061643

    A characteristic feature of gene expression in eukaryotes is the addition of a 5'-terminal 7-methylguanine cap (m7GpppN) to nascent pre-mRNAs in the nucleus catalyzed by capping enzyme and cap methyltransferase. Small interfering RNA (siRNA) knockdown of cap methyltransferase in HeLa cells resul...
  10. Functional interactions of RNA-capping enzyme with factors that positively and negatively regulate promoter escape by RNA polymerase II.

    PNAS 101(20):7572 (2004) PMID 15136722 PMCID PMC419647

    Capping of the 5' ends of nascent RNA polymerase II transcripts is the first pre-mRNA processing event in all eukaryotic cells. Capping enzyme (CE) is recruited to transcription complexes soon after initiation by the phosphorylation of Ser-5 of the carboxyl-terminal domain of the largest subunit...
  11. The Tat/TAR-dependent phosphorylation of RNA polymerase II C-terminal domain stimulates cotranscriptional capping of HIV-1 mRNA.

    PNAS 100(22):12666 (2003) PMID 14569024 PMCID PMC240675

    The HIV type 1 (HIV-1) Tat protein stimulates transcription elongation by recruiting P-TEFb (CDK9/cyclin T1) to the transactivation response (TAR) RNA structure. Tat-induced CDK9 kinase has been shown to phosphorylate Ser-5 of RNA polymerase II (RNAP II) C-terminal domain (CTD). Results presente...
  12. mRNA capping enzyme requirement for Caenorhabditis elegans viability.

    Journal of Biological Chemistry 278(16):14168 (2003) PMID 12576475

    Capping of the initiated 5' ends of RNA polymerase II products is evolutionarily and functionally conserved from yeasts to humans. The m(7)GpppN cap promotes RNA stability, processing, transport, and translation. Deletion of capping enzymes in yeasts was shown to be lethal due to rapid exonucleo...
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  13. Viral and cellular mRNA capping: Past and prospects

    Advances in Virus Research 55:135 (2000)

    This chapter focuses on the history of the discovery of cap and an update of research on viral and cellular-messenger RNA (mRNA) capping. Cap structures of the type m7 GpppN(m)pN(m)p are present at the 5′ ends of nearly all eukaryotic cellular and viral mRNAs. A cap is added to cellula...