The role of SMN protein in microRNA biogenesis

Tese de mestrado. Biologia (Biologia Molecular e Genética). Universidade de Lisboa, Faculdade de Ciências, 2013A Atrofia Muscular Espinal (AME) é uma doença neuromuscular caracterizada pela degeneração dos neurónios alfa motores inferiores, atrofia muscular e perda de função motora. AME é causada por uma mutação homozigótica ou deleção no gene Survival Motor Neuron-1 (SMN1). No entanto, é desconhecida ainda a razão pela qual a perda de função da proteína SMN afecta especificamente os neurónios motores inferiores. Os microRNAs (miRNA) são uma categoria de RNA não codificante expressos em grande quantidade no sistema nervoso. Foi demonstrado que desregulações na expressão dos miRNAs estão associadas a algumas doenças neurológicas, incluindo AME. Especificamente, detectámos um aumento na expressão do microRNA-183 (miR-183) em neurónios com expressão nula da proteína SMN. Desta forma, como objectivo de estudo pretendemos descobrir quais os mecanismos que estão envolvidos na desregulação da expressão dos microRNAs causada pela perda de SMN. Uma vez estando o complexo SMN envolvido no processamento de RNA, foi posto em questão um possível envolvimento deste complexo na regulação da expressão dos microRNAs. Para testar esta hipótese, analisámos o processo de biogénese dos miRNAs desde a sua transcrição primária até aos restantes passos do processamento de RNA, em medula espinal de um modelo animal de AME. A análise de expressão feita ao cluster miR-183~96~182 mostrou uma desregulação na regulação do processo de biogénese deste cluster em neurónios onde a proteína SMN não é expressa. Da mesma forma, verificámos uma desregulação na expressão dos genes envolvidos na biogénese, estabilidade e decaimento dos miRNAs em medula espinhal de um modelo animal de AME. Assim, os resultados obtidos confirmam que a expressão dos miRNAs é alterada devido a níveis deficientes da proteína SMN.Spinal muscular atrophy (SMA) is a neuromuscular disease caused by degeneration of alpha lower motor neurons, muscle atrophy and loss of motor function. SMA occurs when SMN1 (survival motor neuron-1) is homozygously mutated or deleted. However, it remains unclear how deficiency of SMN function mainly affects lower motor neurons. microRNA (miRNA) are a sub-set of non-coding RNAs highly expressed in the nervous system. It has been reported that dysregulation of miRNA expression is associated to several neurological diseases including SMA. We found that expression of miR-183 is elevated in SMN deficient neurons. Therefore, we sought to uncover the mechanisms underlying the dysregulation of miRNA expression caused by SMN loss. Since the SMN complex plays a role in RNA processing, we hypothesize that this complex is involved in regulation of miRNA expression. To test our hypothesis, we analyzed miRNA biogenesis from primary transcript to down-stream steps of RNA processing in spinal cord of SMA mouse model. Analysis of the expression of miR-183~96~182 cluster suggests that the biogenesis process for this cluster is dysregulated in SMN deficient neurons. We found that the genes involved in miRNA biogenesis, stability and decay pathways are dysregulated in spinal cord of SMA mouse model. Our findings suggest that SMN deficiency causes dysregulation of miRNA biogenesis and decay pathways

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora