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Rocaglamide A (RocA) typifies a class of protein synthesis inhibitors that selectively kill aneuploid tumour cells and repress translation of specific messenger RNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase; its messenger RNA selectivity is proposed to reflect highly structured 5' untranslated regions that depend strongly on eIF4A-mediated unwinding. However, rocaglate treatment may not phenocopy the loss of eIF4A activity, as these drugs actually increase the affinity between eIF4A and RNA. Here we show that secondary structure in 5' untranslated regions is only a minor determinant for RocA selectivity and that RocA does not repress translation by reducing eIF4A availability. Rather, in vitro and in cells, RocA specifically clamps eIF4A onto polypurine sequences in an ATP-independent manner. This artificially clamped eIF4A blocks 43S scanning, leading to premature, upstream translation initiation and reducing protein expression from transcripts bearing the RocA-eIF4A target sequence. In elucidating the mechanism of selective translation repression by this lead anti-cancer compound, we provide an example of a drug stabilizing sequence-selective RNA-protein interactions.
Pubmed ID: 27309803 RIS Download
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The Damon Runyon Cancer Research Foundation funds early career cancer researchers who have the energy, drive and creativity to become leading innovators in their fields. We identify the best young scientists in the nation and support them through four award programs: our Fellowship, Pediatric Cancer Fellowship, Clinical Investigator and Innovation Awards. Damon Runyon awards give young scientists: * Freedom to follow their own ideas, explore new paths and take risks * A prestigious endorsement that attracts further funding, advances their careers and accelerates their research * Guaranteed financial support, sparing them hours applying for grants Since 1946, Damon Runyon has invested more than $240 million in the best young minds in the nation. Our alumni include 11 Nobel Laureates and leaders of major cancer centers across the United States. Many of our 3,300 scientists have gone on to make breakthroughs in the way we prevent, diagnose and treat many forms of cancer. The Damon Runyon Cancer Research Foundation is a registered nonprofit with 501(c)(3) status.
View all literature mentionsThe HFSP supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms; topics range from molecular and cellular approaches to systems and cognitive neuroscience. A clear emphasis is placed on novel collaborations that bring biologists together with scientists from fields such as physics, mathematics, chemistry, computer science and engineering to focus on problems at the frontier of the life sciences. The Trust provides funding for research regarding complex biological systems. It offers research grants, post doc fellowships, career development fellowships, and short- long- and cross- disciplinary fellowships. HFSP funding programs are strictly project-related and begin at the postdoctoral level. We have no support for PhD students nor for travel grants to scientific meetings. Nor do we provide sponsorship or funds to organizers of scientific meetings. Research Grants Research Grants are awarded for novel collaborations involving extensive collaboration among teams of scientists working in different countries and in different disciplines. Two types of grants are available: Young Investigators Grants and Program Grants. Postdoctoral Fellowships Postdoctoral Fellowships are available for scientists who wish to work in foreign laboratories, with emphasis on individuals early in their careers who wish to obtain training in a different field of research. Fellows who return to their home countries or move to an HFSP member country that is different from the Fellowship host country are eligible to apply for a Career Development Award. Long-Term Fellowships are for scientists with a Ph.D. degree in the life sciences who wish to broaden their experience through postdoctoral training abroad. Cross-Disciplinary Fellowships are intended for postdoctoral fellows with a Ph.D. degree in the physical sciences, chemistry, mathematics, engineering and computer sciences who wish to receive training in biology. Career Development Awards Career Development Awards are for former HFSP Long-Term or Cross-Disciplinary Fellows who return to their home country or move to an HFSP member country that is different from the host country of their HFSP Fellowship. The award provides support for initiating the fellows'' first independent laboratory.
View all literature mentionsCollection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.
View all literature mentionsGenotyping software package that provides DNA sizing and quality allele calls for all Applied Biosystems electrophoresis-based genotyping systems. GeneMapper specializes in multiapplication functionality, including amplified fragment length polymorphism, loss of heterozygosity, microsatellite, and SNP genotyping analysis. The software provides remote auto-analysis and command line operation, and allows for multiuser, client-server deployment.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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