Multifaceted Regulation of Translational Readthrough by RNA Replication Elements in a Tombusvirus

Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp) in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i) providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii) mediating cis-preferential replication of viral genomes, and (iii) coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family

Proceedings of the Association for Research in Vision and Ophthalmology and Champalimaud Foundation Ocular Oncogenesis and Oncology Conference

Ophthalmic researc

Response criteria for intraocular retinoblastoma: RB-RECIST

Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response—such as progression-free survival—to evaluate the efficacy of treatment agents. Herein, we propose specific criteria for evaluating treatment response of retinoblastoma, the most common pediatric intraocular cancer, and emphasize a multimodal imaging approach for comprehensive assessment of retinoblastoma tumors in clinical trials.Fil: Berry, Jesse L.. University of Southern California; Estados UnidosFil: Munier, Francis L.. Universite de Lausanne; SuizaFil: Gallie, Brenda L.. University of Toronto; Canadá. University Of Toronto. Hospital For Sick Children; CanadáFil: Polski, Ashley. University of Southern California; Estados UnidosFil: Shah, Sona. University of Southern California; Estados UnidosFil: Shields, Carol L.. Wills Eye Hospital; Estados UnidosFil: Gombos, Dan S.. University of Texas; Estados UnidosFil: Ruchalski, Kathleen. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Stathopoulos, Christina. Universite de Lausanne; SuizaFil: Shah, Rachana. Cancer and Blood Disease Institute at Children’s Hospital Los Angeles; Estados UnidosFil: Jubran, Rima. Cancer and Blood Disease Institute at Children’s Hospital Los Angeles; Estados UnidosFil: Kim, Jonathan W.. Cancer and Blood Disease Institute at Children’s Hospital Los Angeles; Estados UnidosFil: Mruthyunjaya, Prithvi. University of Stanford; Estados UnidosFil: Marr, Brian P.. Columbia University Medical Center; Estados UnidosFil: Wilson, Matthew W.. University of Tennessee Health Science Center,; Estados UnidosFil: Brennan, Rachel C.. No especifíca;Fil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Chintagumpala, Murali M.. Texas Children’s Cancer Center; Estados UnidosFil: Murphree, A. Linn. The Vision Center at Children’s Hospital Los Angeles; Estados Unido

Ethylene in vegetative development: a tale with a riddle

Contents Summary 895 I. Introduction 895 II. A snapshot view on the ethylene biosynthesis and signaling pathway in Arabidopsis 896 III. Autocontrol of ethylene biosynthesis 897 IV. Mechanistic control of ethylene signal components 898 V. The auxinethylene circle 901 VI. Tissue- and cell-type-specific regulation of ethylene 903 VII. Cellular basis of ethylene effects on growth 904 Acknowledgements 906 References 906 Summary The vegetative development of plants is strongly dependent on the action of phytohormones. For over a century, the effects of ethylene on plants have been studied, illustrating the profound impact of this gaseous hormone on plant growth, development and stress responses. Ethylene signaling is under tight self-control at various levels. Feedback regulation occurs on both biosynthesis and signaling. For its role in developmental processes, ethylene has a close and reciprocal relation with auxin, another major determinant of plant architecture. Here, we discuss, in view of novel findings mainly in the reference plant Arabidopsis, how ethylene is distributed and perceived throughout the plant at the organ, tissue and cellular levels, and reflect on how plants benefit from the complex interaction of ethylene and auxin, determining their shape. Furthermore, we elaborate on the implications of recent discoveries on the control of ethylene signaling