Com crio-EM, os cientistas determinam a estrutura do fator chave no controle de qualidade do RNA
Na biologia, livrar-se de coisas pode ser tão importante quanto fazaª-las. Um acaºmulo de células, proteanas ou outras moléculas que não são mais necessa¡rias pode...
![](data:image/jpeg;base64,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)
Resumo gra¡fico. Crédito: Cell (2022). DOI: 10.1016/j.cell.2022.04.016
Na biologia, livrar-se de coisas pode ser tão importante quanto fazaª-las. Um acaºmulo de células, proteanas ou outras moléculas que não são mais necessa¡rias pode causar problemas, então os seres vivos evoluaram de várias maneiras para limpar a casa.
Um excelente exemplo éo exossomo de RNA. As moléculas de RNA desempenham muitos papanãis nas células. Alguns deles são traduzidos em proteanas; outros formam a maquinaria de construção de proteanas de uma canãlula. O exossomo de RNA éuma ma¡quina celular que degrada moléculas de RNA que são defeituosas, prejudiciais ou não mais necessa¡rias. Sem essa microsca³pica Marie Kondo para podar o que não desperta alegria, nossas células se tornariam acumuladoras disfuncionais, incapazes de funcionar.
"As vias de vigila¢ncia e degradação do RNA existem em todas as formas de vida", explica Christopher Lima, presidente do Programa de Biologia Estrutural do Instituto Sloan Kettering. “De bactanãrias a humanos, todos os seres vivos tem mecanismos para monitorar a qualidade do RNA e degrada¡-lo propositalmenteâ€.
Por muito tempo, conta o Dr. Lima, esses caminhos foram considerados, como o trabalho domanãstico, meio chatos. Mas acontece que essas vias de degradação são altamente reguladas e controlam tudo, desde o desenvolvimento embriona¡rio atéa progressão do ciclo celular.
Além disso, erros nessas vias podem levar a muitos tipos de doena§as, do câncer a neurodegeneração.
Em um novo artigo publicado em 9 de junho de 2022 na Cell , Dr. Lima e M. Rhyan Puno, pa³s-doutorando no laboratório de Lima, apresentam descobertas que ajudam a explicar como o exossomo de RNA localiza o RNA que precisa ser degradado. Com a ajuda da microscopia eletra´nica criogaªnica (crio-EM), um tipo avana§ado de tecnologia de imagem, os cientistas conseguiram decifrar a estrutura de um conjunto de proteanas chamado Complexo Nuclear Exosome Targeting (NEXT), que éuma parte fundamental da degradação maquinaria.
"Sabaamos que o NEXT tem como alvo e entrega RNA ao exossomo, mas bioquimicamente e estruturalmente, não tanhamos ideia de como ele se parece ou como funciona", diz o Dr. Puno.
Agora, com o crio-EM, os cientistas obtiveram as primeiras imagens natidas do NEXT ligado ao RNA. Essas imagens, em conjunto com os experimentos bioquímicos e biola³gicos, oferecem dicas sobre como as moléculas de RNA são entregues ao exossomo para destruição.
Aproximando-se de uma estrutura
Va¡rios anos atrás, o Dr. Puno começou a estudar a estrutura do NEXT usando a então abordagem padra£o-ouro da cristalografia de raios-X. Nesse manãtodo, as proteanas são primeiro transformadas em cristais, com todas as proteanas alinhadas da mesma maneira. Em seguida, os raios-X são passados ​​atravanãs dos cristais e o padrãode raios-X que atingem um detector pode ser interpretado para determinar a estrutura da proteana.
Â
Enquanto o Dr. Puno foi capaz de cristalizar a proteana NEXT, as imagens de difração de raios-X resultantes não foram boas o suficiente para ver detalhes da estrutura.
"Mas então veio a revolução crio-EM", diz ele. "Cryo-EM nos ajudou a visualizar como essa proteana se parece e como ela se liga a seus substratos de RNA".
Visualizando proteanas em movimento
O Cryo-EM funciona capturando muitas imagens diferentes de uma amostra congelada, mas não cristalizada, de uma proteana e, em seguida, usando manãtodos computacionais para alinha¡-las em uma imagem natida finalizada.
"a‰ quase como capturar um monte de fotos de um pa¡ssaro em voo", diz o Dr. Lima. "Ha¡ todos os tipos de movimentos confusos e as asas do pa¡ssaro podem parecer embaa§adas. Mas se pudermos encontrar partes da asa em todas essas imagens diferentes, podemos alinhar as imagens para reconstruir a aparaªncia das asas do pa¡ssaro e determinar como elas se parecem. trabalhar."
A partir das imagens crio-EM, os cientistas puderam ver que as proteanas NEXT formam um damero muito flexavel oso que significa que duas ca³pias das proteanas NEXT se unem como uma unidade funcional.
"Isso foi muito, muito intrigante", diz o Dr. Puno, observando que a formação de dameros não foi visualizada antes para esses tipos de proteanas.
"A partir de experimentos bioquímicos que realizamos, sabemos que a dimerização éde alguma forma importante para a degradação", continua ele. “Mas ainda éum mistério para noso papel que o damero desempenha na orientação do RNA para o exossomoâ€.
Para ajudar a resolver o mistanãrio, eles esperam capturar o complexo NEXT interagindo em diferentes etapas do processo de degradação e, em seguida, visualizar essas conformações com crio-EM.
Degradação de RNA e doena§a
Ha¡ grandes apostas envolvidas. Uma indicação de quanto importante éa degradação do RNA vem da longa lista de doenças que resultam de degradação defeituosa ou mal controlada. Talvez o exemplo mais famoso seja a fibrose castica. Nesse caso, o RNA mensageiro que codifica uma proteana que transporta aons atravanãs das membranas celulares édegradado pelas vias de decaimento do RNA. Como resultado, a proteana não estãopresente nas membranas mucosas dos pulmaµes, o que leva a um acaºmulo de muco e resulta em respiração severamente prejudicada.
"a‰ um exemplo famoso de controle de qualidade de RNA com resultados ruins", diz o Dr. Lima.
Mas defeitos nas vias de degradação do RNA também desempenham um papel em vários tipos de ca¢ncer. De fato, duas das mutações genanãticas que a plataforma de testes genanãticos da MSK, MSK-IMPACT, testa são encontradas em genes relacionados a via de exossomos de RNA, incluindo uma proteana em NEXT.
E não éapenas o RNA mensageiro que precisa de um controle de qualidade adequado, explica o Dr. Lima.
"A realidade éque se vocêtem vias de controle de qualidade de RNA defeituosas, seus ribossomos não funcionam, seus RNAs de transferaªncia não funcionam, seus spliceossomos não funcionam." A lista continua e continua.
A amplitude de funções que o RNA desempenha explica por que as vias de degradação de RNA defeituosas podem ter esses efeitos causadores de doenças em cascata.
Dar sentido a esses efeitos exigira¡ uma compreensão mais profunda e extensa não apenas do pra³prio exossomo de RNA, mas também das proteanas "upstream", como NEXT, que ajudam a vigiar o RNA e decidir quando um RNA édefeituoso ou não émais necessa¡rio.
"O sonho éiniciar a reação de degradação do RNA, colocar a amostra no crio-EM e realmente ver todas as confirmações possaveis enquanto estãofazendo seu trabalho", diz o Dr. Lima. "Como bia³logos estruturais, queremos ser capazes de ver os processos em ação e depois remonta¡-los."