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La exonización de elementos transponibles genera un depósito de isoformas de proteínas evolutivas y funcionales

Yago A Arribas¹, Blandine Baudon¹, Maxime Rotival²

¹Institut Curie, PSL University, Inserm U932, Immunity and Cancer, 75005 Paris, France.

|December 12, 2024

Resumen

Los elementos transponibles (TE) se pueden empalmar en nuevas isoformas de proteínas, lo que aumenta la diversidad del proteoma humano. Estas isoformas TE-esplicadas funcionales, aunque de baja expresión, se conservan en los individuos y pueden ser moldeadas por la selección natural.

Área de la Ciencia:

La genómica
Biología molecular
Biología evolutiva

Sus antecedentes:

El empalme alternativo genera diversidad de proteínas, incluso a través de la exonización de elementos transponibles (TE).
La relevancia biológica y la contribución proteómica de las transcripciones TE-esplicadas no anotadas siguen siendo en gran medida desconocidas.

Objetivo del estudio:

Caracterizar una población de isoformas TE-exonizantes no anotadas generadas por splicing de ARNm.
Investigar su prevalencia, eficiencia de traducción y relevancia funcional en poblaciones humanas.

Principales métodos:

El ensamblaje del transcriptoma
Perfiles de los ribosomas
Proteomía
Análisis funcionales

Principales resultados:

Se identificaron 1.227 isoformas TE-exonizantes no anotadas, recurrentes en las poblaciones humanas.
Estas isoformas se traducen de manera eficiente, se expresan de manera estable y exhiben una localización celular específica, a veces con funciones modificadas.
Los TE exonizados son a menudo antiguos, asociados con sitios de empalme recientes y contribuyen a la estructura secundaria de isoformas.

Conclusiones:

Las isoformas empalmadas con TE representan un reservorio significativo de diversidad de proteínas funcionales.
Estas isoformas están sujetas a la selección natural, destacando su importancia evolutiva.

Palabras clave:

Sitios de empalme crípticos Nacimiento exón Proteoma no canónico Evolución de las proteínas Isoformas de proteínas Estructura de las proteínas Proteomía Perfilamiento de los ribosomas Elementos transponibles empalme sin anotación

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