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Inhibición específica de la síntesis de poli (A) asociada a la cromatina in vitro por el 5'-trifosfato de cordicépina
K M Rose1, L E Bell, S T Jacob
1Department of Pharmacology, Milton S. Hershey Medical Centre, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA.
Nature
|May 12, 1977
Resumen
El 5'-trifosfato de cordicépina (3'dATP) inhibe selectivamente la poliadenilación inicial del ARNm in vitro. Este fármaco también inhibe la síntesis de ARN, siendo la ARN polimerasa I ligada a la cromatina más sensible que la ARN polimerasa II.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
- Regulación de la expresión génica Regulación de la expresión génica
Sus antecedentes:
- Los ARNm eucariotas poseen tractos poli (ácido adénico) en sus 3'-terminales, cruciales para la estabilidad y la traducción del ARNm.
- La poliadenilación de ARNm ocurre post-transcripcionalmente, que implica una adición inicial rápida de residuos de adenilato seguido por una extensión de la cadena más lenta.
- Cordycepin (3 étaire deoxyadenosine) se ha utilizado para inhibir la poliadenilación, pero su especificidad in vivo se debate.
Objetivo del estudio:
- Para investigar la inhibición selectiva de la poliadenilación inicial del ARNm por cordycepina 5 étaire trifosfato (3 étairedATP) in vitro.
- Para determinar si la polimerasa poli (A) asociada a la cromatina es inhibida selectivamente por el 3 étairedATP.
Principales métodos:
- Estudios in vitro utilizando sistemas libres de células para evaluar los efectos del 3 étairedATP en la poliadenilación y la síntesis de ARN.
- Los ensayos de sensibilidad diferencial para la ARN polimerasa I y la ARN polimerasa II a 3 étaired inhibición de la ATP.
Principales resultados:
- Los bajos niveles de 3 étairedATP inhiben selectivamente la reacción inicial de poliadenilación del ARNm in vitro.
- Las concentraciones más altas de 3 étairedATP inhiben tanto la síntesis de ARNm como de ARNr.
- La ARN polimerasa I unida a la cromatina es significativamente más sensible a la inhibición de la ATP de 3 etapas que la ARN polimerasa II unida a la cromatina.
Conclusiones:
- El estudio apoya la hipótesis de que la polipolimerasa asociada a la cromatina está involucrada en la poliadenilación inicial del ARNm y puede ser inhibida selectivamente por 3 étairedATP.
- 3 étairedATP demuestra efectos inhibidores diferenciales en las polimerasas de ARN, con implicaciones para la comprensión de la regulación de la expresión génica.
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