Indiana University-Purdue University Indianapolis (IUPUI) / The G-quadruplexes (G4s) are guanine-rich four-stranded DNA/RNA structures, which have been found throughout the human genome. G4s have been reported to affect chromatin structure and are involved in important biological processes at transcriptional and epigenetic levels. However, the underlying molecular mechanisms and locating of G4 still remain elusive due to the complexity of G4s. Taking advantage of the development of high-throughput sequencing technologies and machine learning approaches, we constructed this comprehensive investigation on G4 structures, including discovery of a novel marker for functional human hematopoietic stem cells and gained interest in G4 structure, exploring association between G4 and genomic factors by incorporating multi-omics data, and development of a deep-learningbased G4 prediction tool with G4 motif. First, we discovered ADGRG1 as a novel marker for functional human hematopoietic stem cells and its regulation through transcription activities. Our interest in G4s was stimulated while the transcription-related investigations. Next, we analyzed the genome-wide distribution properties of G4s and uncovered the associations of G4 with other epigenetic and transcriptional mechanisms to coordinate gene transcription. We explored that different-confidence G4 groups correlated differently with epigenetic regulatory elements and revealed that G4 structures could correlate with gene expression in two opposite ways depending on their locations and forming strands. Some transcription factors were identified to be over-represented with G4 emergence. We found distinct consensus sequences enriched in the G4 feet, with a high GC content in the feet of high-confidence G4s and a high TA content in solely predicted G4 feet. As for the last part, we developed a novel deep-learning-based prediction tool for DNA G4s with G4 motifs. Considering the classical G4 motif, we applied bi-directional LSTM model with attention method, which captures sequential information, and showed good performance in whole-genome level prediction of DNA G4s with the certified G4 pattern. Our comprehensive work investigated G4 with its functions and predictions and provided a better understanding of G4s on multi-omics level and computational information capture riding the wave of deep learning. / 2023-04-03

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<p>  </p> <p>Protein methylation is one of the most common protein posttranslational modifications (PTMs), within which protein α-N-terminal methylation is largely underexplored. Protein α-N-terminal methylation has been implicated in disease development, including cancer and neurodegenerative diseases, but the physiological and pathological roles of this PTM is not well understood. Protein α-N-terminal methylation modifies the free α-amino group on the protein N-termini and adds between one and three methyl groups by α-N-terminal methyltransferases. It has been shown that protein α-N-terminal methylation is conserved across prokaryotes and eukaryotes. The identification and characterization of the two α-N-terminal methyltransferases in humans, NTMT1 and NTMT2, and their homolog in yeast, Tae1, shows a high conserved substrate recognition and possible shared biological roles. α-N-terminal methyltransferases in humans and yeast recognize substrates with a canonical N-terminal motif, X1-P2-[K/R]3 (X=A, S, P or G after the initial M is cleaved). However, most of the proteins containing the canonical motif have not been studied and identified as substrates. In this study, we use a yeast as a model to explore the substrate members in the protein α-N-terminal methylome and understand the potential regulatory mechanisms. </p> <p>We characterized the yeast phenotypes associated with a <em>TAE1 </em>deletion strain, including increased resistance to heat stress, oxidative stress and paromomycin, and increased sensitivity to benomyl. We also extended the substrate repertoire by validating the presence of α-N-terminal methylation on six substrates by mass spectrometry. Furthermore, we investigate how α-N-terminal methylation could regulate Hsp31, a multifunctional heat shock protein that is associated with yeast heat response and oxidative response. Results suggest that methylation might regulate the localization of Hsp31, rather than directly regulating Hsp31 chaperone activity or methylglyoxalase activity. Alternatively, we developed another methodology to explore the α-N-terminal methylome without motif restriction by repurposing public mass spectrometry datasets for α-N-terminal methylation events in both yeast and humans. We found about 1-2 % of the total proteome are α-N-terminally methylated. Interestingly, the majority of the α-N-terminal methylation events were not on the canonical motif sequence. This indicates a more prevalent existence of α-N-terminal methylation.</p>

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The introduction of N2-fixing trees in mixed forest systems is a recent strategy that can reduce the use of external inputs and increase the Eucalyptus plantations sustainability. In these systems, there is a strong interconnection between the trees, which occurs through a complex network of interactions between microorganisms, above and belowground. These interactions result in innumerable biological functions and ecosystem services, which are essential for soil and plant health. Moreover, the result of the Eucalyptus-microbiome-Acacia interaction has been pointed out as essential in achieving higher Eucalyptus productivity indexes in mixed systems. Our aim was to explore the dynamics of microbiome related to nutrient cycling in pure and mixed Eucalyptus grandis and Acacia mangium plantations. Specifically, our efforts were focused on the microbiome benefits to the biological functions improvement in commercial Eucalyptus plantations driving by Acacia introduction in the system. We also give details regarding as the knowledge of the microbiome diversity, composition and functions can help us to understand their close relationship with carbon (C) and nitrogen (N) cycling in soil and litter layers. We believe that holistic approaches in which we can explore the biological interactions in systems using plants of high ecological value (Acacia) and high economic value (Eucalyptus) will be inevitable in the near future. If we learn how to manipulate important processes mediated by the microbiome involved in these interactions, we will take an important step to overcome the current resource constraints, combining increased productivity with the ecological intensification of forest plantations and the environmental sustainability. / A inserção de árvores fixadoras de nitrogênio (N2) em sistemas florestais mistos é uma estratégia recente que pode reduzir o uso de inputs externos e aumentar a sustentabilidade das plantações de Eucalipto. Nesses sistemas, existe uma forte interconexão entre as árvores, a qual ocorre por uma complexa rede de interações entre micro-organismos, acima e abaixo do solo. Essas interações resultam em inúmeros processos biológicos e serviços ecossistêmicos, os quais são essenciais para a saúde do solo e das plantas. Além do mais, o resultado da interação Eucalipto-microbioma-Acácia tem sido apontado como essencial no alcance de maiores índices de produtividade do Eucalipto em sistemas mistos. Nosso objetivo foi explorar a dinâmica do microbioma relacionado à ciclagem de nutrientes em plantações puras e mistas de Eucalyptus grandis e Acacia mangium. Especificamente, nossos esforços focaram nos benefícios do microbioma para a melhoria de funções biológicas, principalmente aquelas promovidas pela introdução da Acácia em plantações comerciais de Eucalipto. Por exemplo, abordamos detalhes como o conhecimento da diversidade, composição e funções desse microbioma pode nos ajudar a compreender sua íntima relação com a ciclagem de carbono (C) e nitrogênio (N) no solo e na serapilheira. Acreditamos que abordagens holísticas, com as quais possamos explorar as interações biológicas em sistemas com plantas de alto valor ecológico (Acácia) e alto valor econômico (Eucalipto) serão inevitáveis no futuro. Se aprendermos a manipular alguns processos mediados pelo microbioma envolvido nessas interações, daremos um passo importante para superar as atuais limitações de recursos, aliando o aumento da produtividade com a intensificação ecológica das plantações florestais e a sustentabilidade do meio ambiente.

The introduction of N2-fixing trees in mixed forest systems is a recent strategy that can reduce the use of external inputs and increase the Eucalyptus plantations sustainability. In these systems, there is a strong interconnection between the trees, which occurs through a complex network of interactions between microorganisms, above and belowground. These interactions result in innumerable biological functions and ecosystem services, which are essential for soil and plant health. Moreover, the result of the Eucalyptus-microbiome-Acacia interaction has been pointed out as essential in achieving higher Eucalyptus productivity indexes in mixed systems. Our aim was to explore the dynamics of microbiome related to nutrient cycling in pure and mixed Eucalyptus grandis and Acacia mangium plantations. Specifically, our efforts were focused on the microbiome benefits to the biological functions improvement in commercial Eucalyptus plantations driving by Acacia introduction in the system. We also give details regarding as the knowledge of the microbiome diversity, composition and functions can help us to understand their close relationship with carbon (C) and nitrogen (N) cycling in soil and litter layers. We believe that holistic approaches in which we can explore the biological interactions in systems using plants of high ecological value (Acacia) and high economic value (Eucalyptus) will be inevitable in the near future. If we learn how to manipulate important processes mediated by the microbiome involved in these interactions, we will take an important step to overcome the current resource constraints, combining increased productivity with the ecological intensification of forest plantations and the environmental sustainability. / A inserção de árvores fixadoras de nitrogênio (N2) em sistemas florestais mistos é uma estratégia recente que pode reduzir o uso de inputs externos e aumentar a sustentabilidade das plantações de Eucalipto. Nesses sistemas, existe uma forte interconexão entre as árvores, a qual ocorre por uma complexa rede de interações entre micro-organismos, acima e abaixo do solo. Essas interações resultam em inúmeros processos biológicos e serviços ecossistêmicos, os quais são essenciais para a saúde do solo e das plantas. Além do mais, o resultado da interação Eucalipto-microbioma-Acácia tem sido apontado como essencial no alcance de maiores índices de produtividade do Eucalipto em sistemas mistos. Nosso objetivo foi explorar a dinâmica do microbioma relacionado à ciclagem de nutrientes em plantações puras e mistas de Eucalyptus grandis e Acacia mangium. Especificamente, nossos esforços focaram nos benefícios do microbioma para a melhoria de funções biológicas, principalmente aquelas promovidas pela introdução da Acácia em plantações comerciais de Eucalipto. Por exemplo, abordamos detalhes como o conhecimento da diversidade, composição e funções desse microbioma pode nos ajudar a compreender sua íntima relação com a ciclagem de carbono (C) e nitrogênio (N) no solo e na serapilheira. Acreditamos que abordagens holísticas, com as quais possamos explorar as interações biológicas em sistemas com plantas de alto valor ecológico (Acácia) e alto valor econômico (Eucalipto) serão inevitáveis no futuro. Se aprendermos a manipular alguns processos mediados pelo microbioma envolvido nessas interações, daremos um passo importante para superar as atuais limitações de recursos, aliando o aumento da produtividade com a intensificação ecológica das plantações florestais e a sustentabilidade do meio ambiente.