RESUMO
Plant ARGONAUTE (AGO) proteins play pivotal roles regulating gene expression through small RNA (sRNA) -guided mechanisms. Among the 10 AGO proteins in Arabidopsis thaliana, AGO1 stands out as the main effector of post-transcriptional gene silencing. Intriguingly, a specific region of AGO1, its N-terminal extension (NTE), has garnered attention in recent studies due to its involvement in diverse regulatory functions, including subcellular localization, sRNA loading and interactions with regulatory factors. In the field of post-translational modifications (PTMs), little is known about arginine methylation in Arabidopsis AGOs. In this study, we show that NTE of AGO1 (NTEAGO1) undergoes symmetric arginine dimethylation at specific residues. Moreover, NTEAGO1 interacts with the methyltransferase PRMT5, which catalyzes its methylation. Notably, we observed that the lack of symmetric dimethylarginine has no discernible impact on AGO1's subcellular localization or miRNA loading capabilities. However, the absence of PRMT5 significantly alters the loading of a subgroup of sRNAs into AGO1 and reshapes the NTEAGO1 interactome. Importantly, our research shows that symmetric arginine dimethylation of NTEs is a common process among Arabidopsis AGOs, with AGO1, AGO2, AGO3 and AGO5 undergoing this PTM. Overall, this work deepens our understanding of PTMs in the intricate landscape of RNA-associated gene regulation.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arginina , Proteínas Argonautas , Processamento de Proteína Pós-Traducional , Proteína-Arginina N-Metiltransferases , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Metilação , Arginina/metabolismo , Regulação da Expressão Gênica de Plantas , MicroRNAs/metabolismo , MicroRNAs/genética , Ligação ProteicaRESUMO
Maximum points of breast density have been strongly associated with breast cancer masking than global breast density, which is a widely used measure today. The objective of this work was to verify the correlation between two measures of global breast density (VBDGLOBAL and DABGLOBAL) and a measure of maximum point breast density (VBDMP). Mammographic images of 4.020 patients were analyzed using the Volpara software, which calculated or extracted the variables needed for the study from the DICOM header. Two-tailed partial correlation tests were performed between the variable VBDGLOBAL with VBDMP and DABGLOBAL with VBDMP in the following contexts: keeping PA and CBT constant, keeping only CBT constant, and keeping only PA constant. The Pearson test was also used to verify the bivariate correlation between VBDGLOBAL with VBDMP and DABGLOBAL with VBDMP. For the two-tailed partial correlation tests between VBDGLOBAL with VBDMP, keeping the CBT and PA variables constant resulted in r = 0.845 (p < 0.05). When kept constant only the CBT, r = 0.875 (p < 0.05), and keeping only the PA constant r = 0.866 (p < 0.05). Pearson's test showed r = 0.883 (p < 0.05). For the two-tailed partial correlation tests between the DABGLOBAL with VBDMP quantities, the results were r = 0.675 (p < 0.05), r = 0.725 (p < 0.05) and r = 0.701 (p < 0.05) for constant CBT and PA, constant CBT and constant PA, respectively, while the Pearson test resulted in r = 0.738 (p < 0.05). We conclude that a woman who has high global breast density is also highly likely to have maximum points of breast density.
Assuntos
Densidade da Mama , Neoplasias da Mama , Humanos , Feminino , Brasil , Mamografia/métodos , SoftwareRESUMO
In many countries, there is an interest in determining the location of the women with the highest breast density. This investigation is important for optimize screening for breast cancer for women with dense breasts as other imaging modalities since 2D mammography is not very efficient on this type of breast. The objective of this study was to evaluate the variations in breast density in Brazilian women of different regions of Brazil. The mammographic images were taken from four regions of Brazil. The images, in the cranial caudal (CC) projection, were separated into intervals of compressed breast thickness (CBT) and patient age and were analysed by the software VolparaDensity, where volumetric breast density (VBD) calculations were performed. For each interval, null hypothesis tests for the mean difference between the VBD from the four regions of Brazil were performed. The paired tests indicated that there was a significant difference in the VBD of the women in the different regions of Brazil, with variations from 11.05% to 36.73%. Higher VBD was observed for women living in the Southeast region, followed by the Midwest, Northeast, and North regions. The Brazilian IBGE data show that the most urbanised region in Brazil is the Southeast, which coincides with the second highest rate of breast cancer in Brazil, according to the Brazilian National Cancer Institute (INCA). It is also known that breast cancer is strongly related to breast density; therefore, the results of this work support the data presented by federal agencies demonstrating that women living in the most urbanised region of Brazil (e.g., Southeast) present the highest breast density.