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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2020.tde-16072020-132627
Document
Author
Full name
Maria Gabriela Pereira dos Santos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Coltri, Patricia Pereira (President)
Amaral, Jonatas Bussador do
Diniz, Gabriela Placoná
Fuziwara, Cesar Seigi
Title in Portuguese
Regulação da biogênese de microRNAs por proteínas hnRNPs.
Keywords in Portuguese
MicroRNAs
MiR-17-92
Proteínas hnRNPs
RNA
Splicing
Abstract in Portuguese
O splicing é um processo crítico para expressão gênica em eucariotos, pois os genes são transcritos como pré-mRNAs, os quais são compostos por exons (sequências que permanecem nos mRNAs maduros) e introns (sequências intermediárias). O processo de splicing envolve a excisão de introns e a ligação de exons, resultando em transcritos maduros (mRNA). Este processo é realizado por uma maquinaria complexa chamada spliceossomo, que é composta por cinco pequenos RNAs associados a proteínas (snRNAs) e mais de 100 proteínas, sendo que algumas podem associar-se transitoriamente a componentes de spliceossomo ou aos pré-mRNAs. As hnRNPs são proteínas que podem associar-se ao complexo spliceossomo, desempenhando um papel regulador nos locais de splicing,/i> e frequentemente envolvidas na mediação de splicing alternativo. No genoma humano, mais de 70% dos miRNAs estão localizados em introns, portanto, é possível que o processo de splicing seja importante para sua maturação. O aumento da expressão do cluster de miRNAs miR-17-92 já foi relacionado ao desenvolvimento de muitas patologias, como câncer de tireoide, câncer de pulmão e linfoma. Estudos anteriores mostraram que a hnRNP A1 é importante para a maturação de do miR-18a. Neste trabalho nós investigamos a potencial associação das proteínas hnRNP A1 e hnRNP G aos miRNAs do cluster miR-17-92. Os resultados mostraram que a hnRNP A1 está associada a outros membros do cluster miR-17-92, e que a superexpressão dessa proteína aumenta as capacidades proliferativa, migratória e invasiva em células de câncer papilífero de tireóide, BCPAP.
Title in English
Regulation of microRNAs biogenesis by hnRNP proteins.
Keywords in English
HnRNPs proteins
MicroRNAs
MiR-17-92
RNA
Splicing
Abstract in English
Splicing is a critical process for gene expression in eukaryotes, as genes are transcribed as pre-mRNAs, which are composed of exons (sequences that remain in mature mRNAs) and introns (intermediate sequences). The splicing process involves intron excision and junction of exons, resulting in mature transcripts (mRNA). This process is performed by a complex machinery called spliceosome, which is composed by five snRNAs and more than 100 proteins, some of which may transiently associate with spliceosome components or pre-mRNAs. HnRNPs are proteins that can associate with the spliceosome complex, playing a regulatory role at splicing sites and often involved in alternative splicing mediation. In the human genome, over 70% of miRNAs are located in introns, therefore, it is possible that the splicing process is important for their maturation. Increased miR-17-92 cluster expression levels have been related to the development of many pathologies, such as thyroid cancer, lung cancer and lymphoma. Previous studies have shown that hnRNP A1 is important for miR-18a maturation. We investigated the potential association of hnRNP A1 and hnRNP G proteins with miRNAs from the miR-17-92 cluster. The results showed that hnRNP A1 is associated with other members of the miR-17-92 cluster, and that overexpression of this protein increases the proliferative, migratory and invasive capabilities of papillary thyroid cancer cells, BCPAP.
 
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Release Date
2022-07-16
Publishing Date
2021-10-14
 
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