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Los genes de ARN pequeño (EBER) del virus de Epstein-Barr: unidades de transcripción únicas que combinan los

J G Howe¹, M D Shu

¹Howard Hughes Medical Institute, Department of Molecular Biophysics and Biochemistry, New Haven, Connecticut 06510.

|June 2, 1989

Resumen

Los genes de ARN pequeño (EBER) codificados por el virus de Epstein-Barr utilizan elementos promotores únicos, incluidos los sitios de unión ATF y Sp1, para la expresión de alto nivel. Estos hallazgos revelan nuevos mecanismos reguladores para la transcripción de la ARN polimerasa III en células transformadas por el EBV.

Área de la Ciencia:

Biología Molecular Biología Molecular
Virología Virología.
Reglamento genético Reglamento genético.

Sus antecedentes:

Los ARN pequeños codificados por el virus de Epstein-Barr (EBER) son transcripciones abundantes en las células infectadas.
Su regulación transcripcional precisa y sus elementos promotores siguen siendo incompletamente comprendidos.
Los EBER representan una clase única de transcripciones de la ARN polimerasa III.

Objetivo del estudio:

Para dilucidar los elementos promotores y los factores de transcripción que rigen la expresión génica EBER.
Comprender los mecanismos detrás de la expresión de alto nivel de EBER en linfocitos transformados por EBV.

Principales métodos:

Análisis de las regiones promotoras de genes EBER, incluidas las regiones de control intragénico (cajas A y B) y los elementos aguas arriba.
Ensayos de huella de ADNasa I para identificar las interacciones proteína-ADN.
Los ensayos de competencia de oligonucleótidos confirman la unión al factor de transcripción.

Principales resultados:

Los genes EBER poseen regiones funcionales de control intragénico de caja A y B.
Se identificaron tres elementos aguas arriba, estimulando la expresión in vivo hasta 50 veces.
La huella de la DNAasa I reveló la unión del factor de transcripción activador (ATF) o proteínas relacionadas con los nucleótidos -40 a -55.
Proteína Sp1 o proteínas relacionadas unidas a los nucleótidos -56 a -77.
Un elemento entre las posiciones -23 y -28 se parecía a una caja TATA.

Conclusiones:

Los EBER son transcripciones inusuales de ARN polimerasa III reguladas por distintos elementos promotores.
Los factores de transcripción ATF y Sp1-like juegan un papel crucial en el control de la expresión EBER.
Es probable que estos mecanismos reguladores contribuyan a la alta abundancia de EBER en las células transformadas por EBV.

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