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Caracterização da expressão do gene ZFP36L1 associado a mecanismos de patogénese da osteoartrose e osteoporose
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Abstract(s)
O organelo sem membrana, designado como grânulo TIS, é caracterizado pela interação da proteína ZFP36 ring finger protein like 1 (ZFP36L1), também conhecida como TIS11B, com mRNAs que codificam proteínas membranares. ZFP36L1 promove o enriquecimento ou exclusão de transcritos, dependendo do tamanho dos seus 3'UTR e número de elementos ricos em adeninas (A) e uracilos (U) (AREs). A associação de grânulos TIS à superfície do retículo endoplasmático cria um microambiente que favorece a tradução e localização de proteínas específicas na superfície da membrana das células. ZFP36L1 também é conhecido por regular a estabilidade e degradação de transcritos de vários genes alvo, como é o caso de vários intermediários inflamatórios, o que sugere um papel duplo para o ZFP36L1, favorecendo a transcrição de proteínas membranares e destabilizando outros alvos. Para além dos marcadores de inflamação, também regula os intermediários da via de sinalização das BMPs e está envolvido em mecanismos de senescência o impacto do ZFP36L1 nas células precursoras de osteoblastos e de condrócitos e na sua diferenciação terminal é praticamente desconhecido. Recentemente, o ZFP36L1 tem sido implicado na promoção da diferenciação de osteoblastos e a sua expressão foi identificada como sendo diminuída em ratinhos mais idosos, resultando numa diferenciação preferencial das células mesenquimais para a linhagem adipocitária. Também foi publicado que o aumento da expressão de ZFP36L1 está associado aos mecanismos de progressão da osteoartrose. Este projeto tem como objetivo a identificação, compilação e discussão de estudos publicados que descrevem a expressão de ZFP36L1 em contextos patológicos associados ao desenvolvimento de osteoporose e osteoartrose, focando a discussão dos resultados obtidos no impacto que ZFP36L1 pode ter no metabolismo do osso e da cartilagem. Através da pesquisa da base de dados Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geoprofiles) e bibliografia associada vai-se procurar compilar e comparar dados relativos à expressão de ZFP36L1 em experiências usando tecidos de humano e de ratinho. Com base nesses resultados vai-se procurar contextualizar a expressão desta proteína nos mecanismos associados ao desenvolvimento de osteoartrose e osteoporose. Serão igualmente estudadas (i) as relações filogenéticas destes genes nas principais espécies utilizadas como modelos biológicos em ciências biomédicas, e (ii) a presença de polimorfismos no gene que codifica para a ZFP36L1 e possam ser associados a patologias no sistema musculoesquelético e contextualizar os resultados relativamente às funções das proteínas codificadas.
The membrane-free organelle, called the TIS granule, is characterized by the interaction of the protein ZFP36 ring finger protein like 1 (ZFP36L1), also known as TIS11B, with mRNAs that encode membrane proteins. ZFP36L1 promotes enrichment or deletion of transcripts, depending on the size of its 3'UTR and number of adenine (A) and uracil (U) rich elements (AREs). The association of TIS granules to the surface of the endoplasmic reticulum creates a microenvironment that favors the translation and localization of specific proteins on the surface of the cell membrane. ZFP36L1 is also known to regulate the stability and degradation of transcripts of several target genes, as is the case of several inflammatory intermediates, which suggests a dual role for ZFP36L1, favoring the transcription of membrane proteins and destabilizing other targets. In addition to inflammation markers, it also regulates the intermediaries of the BMPs signaling pathway and is involved in senescence mechanisms. The impact of ZFP36L1 on precursor cells of osteoblasts and chondrocytes and on their terminal differentiation is practically unknown. Recently, ZFP36L1 has been implicated in promoting osteoblast differentiation and its expression has been identified to be decreased in older mice, resulting in preferential differentiation of mesenchymal cells towards the adipocyte lineage. It has also been published that increased expression of ZFP36L1 is associated with mechanisms of osteoarthritis progression. This project aims to identify, compile and discuss published studies that describe the expression of ZFP36L1 in pathological contexts associated with the development of osteoporosis and osteoarthritis, focusing on the discussion of the results obtained in the impact that ZFP36L1 may have on bone and cartilage metabolism. Searching the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geoprofiles) and associated bibliography will attempt to compile and compare data relating to ZFP36L1 expression in experiments using human and human tissues. mouse. Based on these results, we will try to contextualize the expression of this protein in the mechanisms associated with the development of osteoarthritis and osteoporosis. Will also be studied (i) the phylogenetic relationships of these genes in the main species used as biological models in biomedical sciences, and (ii) the presence of polymorphisms in the gene that codes for ZFP36L1 and can be associated with pathologies in the musculoskeletal system and contextualize the results with respect to the functions of the encoded proteins.
The membrane-free organelle, called the TIS granule, is characterized by the interaction of the protein ZFP36 ring finger protein like 1 (ZFP36L1), also known as TIS11B, with mRNAs that encode membrane proteins. ZFP36L1 promotes enrichment or deletion of transcripts, depending on the size of its 3'UTR and number of adenine (A) and uracil (U) rich elements (AREs). The association of TIS granules to the surface of the endoplasmic reticulum creates a microenvironment that favors the translation and localization of specific proteins on the surface of the cell membrane. ZFP36L1 is also known to regulate the stability and degradation of transcripts of several target genes, as is the case of several inflammatory intermediates, which suggests a dual role for ZFP36L1, favoring the transcription of membrane proteins and destabilizing other targets. In addition to inflammation markers, it also regulates the intermediaries of the BMPs signaling pathway and is involved in senescence mechanisms. The impact of ZFP36L1 on precursor cells of osteoblasts and chondrocytes and on their terminal differentiation is practically unknown. Recently, ZFP36L1 has been implicated in promoting osteoblast differentiation and its expression has been identified to be decreased in older mice, resulting in preferential differentiation of mesenchymal cells towards the adipocyte lineage. It has also been published that increased expression of ZFP36L1 is associated with mechanisms of osteoarthritis progression. This project aims to identify, compile and discuss published studies that describe the expression of ZFP36L1 in pathological contexts associated with the development of osteoporosis and osteoarthritis, focusing on the discussion of the results obtained in the impact that ZFP36L1 may have on bone and cartilage metabolism. Searching the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geoprofiles) and associated bibliography will attempt to compile and compare data relating to ZFP36L1 expression in experiments using human and human tissues. mouse. Based on these results, we will try to contextualize the expression of this protein in the mechanisms associated with the development of osteoarthritis and osteoporosis. Will also be studied (i) the phylogenetic relationships of these genes in the main species used as biological models in biomedical sciences, and (ii) the presence of polymorphisms in the gene that codes for ZFP36L1 and can be associated with pathologies in the musculoskeletal system and contextualize the results with respect to the functions of the encoded proteins.
Description
Keywords
TIS ZFP36l1 Bmps Gene