A functional study of the conserved LSM proteins in C. elegans reveals their involvement in the stress response of metazoans

Cornes Maragliano, Eric

A functional study of the conserved LSM proteins in C. elegans reveals their involvement in the stress response of metazoans

Document Type

Doctoral thesis
Published Version

Author

Cornes Maragliano, Eric

Director

Cerón Madrigal, Julián

Publication Date

2015-07-24

Pages

176 p.

Citation

Cornes Maragliano, E. A functional study of the conserved LSM proteins in C. elegans reveals their involvement in the stress response of metazoans. Universitat Pompeu Fabra; 2015. handle: http://hdl.handle.net/10803/315473

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

Lsm proteins regulate RNA metabolism and are conserved in the three domains of life, typically functioning as RNA-binding complexes involved in a wide range of post-transcriptional mechanisms. Generally, their functions have been explored in unicellular models using biochemical approaches; however their physiological roles in multicellular organisms remain unknown. This gap in knowledge is biomedically relevant since alterations of individual LSM proteins functions have been related to cancer development. We performed a functional study of the eleven LSM proteins encoded in the C. elegans genome. We found that although lsm-1 and lsm-3 genes are not essential for the viability of the organism, they are required for wild type healthspan. In addition LSM-1 and LSM-3 proteins function in stress responses by promoting cytoplasmic LSM foci formation and influencing Insulin/IGF-like signaling pathway, a major regulator of development and stress response in metazoans. This study uncovers a physiological role for the LSM proteins in multicellular organisms as essential players for healthspan maintenance and stress adaptation.
Las proteínas de la familia Lsm están conservadas desde bacterias a humanos y participan en el metabolismo de ARN. Aunque el estudio de sus funciones ha sido generalmente abordado mediante aproximaciones bioquímicas en modelos unicelulares, sus funciones en organismos multicelulares son desconocidas. Su estudio en organismos modelo es de especial relevancia biomédica ya que la alteración específica de ciertas proteínas Lsm ha sido relacionada con el desarrollo del cáncer. Mediante el estudio funcional de las once proteínas Lsm presentes en C. elegans, mostramos cómo los genes lsm-1 y lsm-3, pese a no ser esenciales para la viabilidad del organismo, son necesarios para el mantenimiento de su salud. Además, LSM-1 y LSM-3 funcionan durante la respuesta a estrés promoviendo la agregación citoplasmática de proteínas LSM y contribuyendo a la correcta señalización a través de la vía de la Insulina/IGF-like, importante en la regulación del metabolismo y la respuesta a estrés en metazoos. Este estudio destaca el importante papel fisiológico de las proteínas LSM en el desarrollo y la adaptación al estrés de un organismo multicelular.