RESUMEN
Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity. We previously showed that DSB-induced small RNAs (diRNAs) facilitate homologous recombination-mediated DSB repair in Arabidopsis thaliana Here, we show that INVOLVED IN DE NOVO2 (IDN2), a double-stranded RNA binding protein involved in small RNA-directed DNA methylation, is required for DSB repair in Arabidopsis. We find that IDN2 interacts with the heterotrimeric replication protein A (RPA) complex. Depletion of IDN2 or the diRNA binding ARGONAUTE2 leads to increased accumulation of RPA at DSB sites and mislocalization of the recombination factor RAD51. These findings support a model in which IDN2 interacts with RPA and facilitates the release of RPA from single-stranded DNA tails and subsequent recruitment of RAD51 at DSB sites to promote DSB repair.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteína de Replicación A/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Roturas del ADN de Doble Cadena , Reparación del ADN/genética , Reparación del ADN/fisiología , Recombinación Homóloga/genética , Recombinación Homóloga/fisiología , Unión Proteica/genética , Unión Proteica/fisiología , Proteínas de Unión al ARN/genética , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , Proteína de Replicación A/genéticaRESUMEN
It is increasingly evident that various RNAs can bind chromatin to regulate gene expression and genome organization. Here we adapted a sequencing-based technique to profile RNA-chromatin interactions at a genome-wide scale in Arabidopsis seedlings. We identified more than 10,000 RNA-chromatin interactions mediated by protein-coding RNAs and non-coding RNAs. Cis and intra-chromosomal interactions are mainly mediated by protein-coding RNAs, whereas inter-chromosomal interactions are primarily mediated by non-coding RNAs. Many RNA-chromatin interactions tend to positively correlate with DNA-DNA interactions, suggesting their mutual influence and reinforcement. We further show that some RNA-chromatin interactions undergo alterations in response to biotic and abiotic stresses and that altered RNA-chromatin interactions form co-regulatory networks. Our study provides a global view on RNA-chromatin interactions in Arabidopsis and a rich resource for future investigations of regulatory roles of RNAs in gene expression and genome organization.
Asunto(s)
Arabidopsis/genética , Arabidopsis/metabolismo , Cromatina/metabolismo , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , ARN de Planta/genética , ARN de Planta/metabolismo , Plantones/genética , Plantones/metabolismo , Estrés Fisiológico/genéticaRESUMEN
This study is to evaluate the association of 9 single nucleotide polymorphisms (SNPs) with Graves' disease (GD) in different homogenous samples of the Chinese Han population. A total of 2,865 unrelated individuals were enrolled from Linyi City, Shandong Province, China, including 1,139 patients of GD and 1,726 controls. All 9 SNPs showed significant associations with GD (P < 1.3×10(-4), Bonferroni corrected Pc < 0.001). The most significant association was detected at rs2281388 at the HLA-DPB1 locus (P=1.3×10(-21); OR=1.62, 95% CI: 1.47-1.79). After adjusting for gender and age, 7 SNPs remained significantly associated with GD (P < 3.4×10(-4), Pc < 0.003). The risk of GD caused by any of these SNPs was not significantly different between female and male participants (Phet > 0.15). Four SNPs located in MHC regions were significantly associated with GD in different ages (P < 8.4×10(-4), Pc < 0.04). The risks of any SNP leading to the development of GD did not differ significantly in different ages (P_trend > 0.02, Pc > 0.18). The rs6457617 at the HLA-DR-DQ locus was significantly correlated with gender in GD patients (P=0.004, Pc =0.04). No significant correlation was found between any SNP and age of diagnosis in GD patients (P > 0.02, Pc > 0.17). The 9 previously identified SNPs are associated with GD in the Chinese Han population. And, gender and age may not influence the associations between the 9 SNPs and GD.