La organización y función del genoma del virus del mosaico dorado del frijol

Programa Cooperativo Regional de Frijol para Centroamérica, México y el Caribe (PROFRIJOL)Cooperación Suiza para el Desarrollo (COSUDE)Centro Internacional de Agricultura Tropical (CIAT)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Estación Experimental Agrícola Fabio Baudrit Moreno (EEAFBM

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

Bean Golden Mosaic: Research Advances

El frijol (Phaseolus vulgaris L.) es una de las fuentes de proteina (15-35%) y calorías (ca. 340 caI./100 gr) más importantes en la América Latina. En esta región, centro de origen de esta especie, se producen más de cuatro millones de toneladas de frijol al año, lo cual equivale al 88% de la semilla de frijol producida en las regiones tropicales del mundo. Brasil, el mayor productor de frijol del mundo, posee un consumo per capita de cerca de 20 kg/año. En America Central, el frijol es igualmente importante, siendo consumido en la mayoría de los países centroamericanos hasta tres veces por día. Proporcionalmente, en la America Central se cultiva el doble del área que en Brasil, relativo a sus extensiones territoriales. El frijol es también producido en islas del Caribe, tales como Cuba (ca. 26.000 TM), Haití (56.000 TM) y República Dominicana (55.000 TM) según datos de 1990 (CIAT). México, el segundo productor de frijol en la America Latina, consume aproximadamente 1.2 millones de toneladas métricas de frijol al año. A pesar de que México cultiva cerca de 1.800.000 hectáreas de frijol, la demanda interna no es satisfecha en algunos años dado la baja productividad del cultivo. Esta baja productividad relativa del frijol, no solo en México sino también en el resto de la América Latina (700 kg/ha vs. 1.600 kg/ha en los Estados Unidos), es una consecuencia de los múltiples problemas bióticos y abióticos que inciden en el cultivo, en el trópico Americano. Es precisamente en las regiones productoras de frijol situadas en climas cálidos, de altitud baja a intermedia (0-1200 m.s.n.m), donde el mosaico dorado del frijol alcanza su mayor incidencia.The common bean (Phaseolus vulgaris L.) is an important source of protein and calories in Latin America. In this region, the center of origin of this legume species, over 4 million tons of dry beans are produced per year. Nevertheless, many Latin American countries, including two of the largest producers of beans in the world, Brazil and Mexico, have to import beans to meet internal demand. This shortage of beans is related to the low productivity of this crop in Latin America (700 kg /ha vs. 1,600 kg/ ha average in the USA). The low productivity in the main bean production regions of tropical America is associated to the incidence of several biotic and abiotic constraints. Among the biotic constraints, bean golden mosaic virus is undoubtedly the main bean production problem in the lowland tropics, particularly, during the dry seasons of the year.Programa Cooperativo Regional de Frijol para Centroamérica, México y el Caribe (PROFRIJOL)Cooperación Suiza para el Desarrollo (COSUDE)Centro Internacional de Agricultura Tropical (CIAT)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Estación Experimental Agrícola Fabio Baudrit Moreno (EEAFBM

RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response

Protein modifications by ubiquitin and small ubiquitin-like modifier (SUMO) play key roles in cellular signaling pathways. SUMO-targeted ubiquitin ligases (STUbLs) directly couple these modifications by selectively recognizing SUMOylated target proteins through SUMO-interacting motifs (SIMs), promoting their K48-linked ubiquitylation and degradation. Only a single mammalian STUbL, RNF4, has been identified. We show that human RNF111/Arkadia is a new STUbL, which used three adjacent SIMs for specific recognition of poly-SUMO2/3 chains, and used Ubc13–Mms2 as a cognate E2 enzyme to promote nonproteolytic, K63-linked ubiquitylation of SUMOylated target proteins. We demonstrate that RNF111 promoted ubiquitylation of SUMOylated XPC (xeroderma pigmentosum C) protein, a central DNA damage recognition factor in nucleotide excision repair (NER) extensively regulated by ultraviolet (UV)-induced SUMOylation and ubiquitylation. Moreover, we show that RNF111 facilitated NER by regulating the recruitment of XPC to UV-damaged DNA. Our findings establish RNF111 as a new STUbL that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response