Expression changes of alg-1 alter the miRNome and increase sensitivity to oxidative stressors in Caenorhabditis elegans

Author(s)

Raíssa de Paula Moro

• Document type: Master's Dissertation
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2019-02-01

Examining board members

Murilo Vieira Geraldo; Fernanda Marques da Cunha

• Advisor: Marcelo Alves da Silva Mori

Abstract

The overall expression of microRNAs (miRNAS) decreases throughout aging on different phylogenetic groups, including Caenorhabditis elegans. However, the exact identity of the mechanism involved in this reduction and its effects on phenotypes associated with aging have not yet been conclusively determined. There is evidence that certain miRNAs regulate C. elegans lifespan, and the ALG-1 argonaute protein is one of the major regulators of biogenesis and function of miRNAs in C. elegans. Therefore, this dissertation consists of the description and interpretation of results from experiments designed to characterize the mechanism of alg-1 transcriptional regulation and its function in the response to oxidative and thermal stress, and longevity of C. elegans, as well as to analyse the pattern of miRNA expression of worms under conditions of either alg-1 overexpression (ALG-1 O/E), or glp-1(e2144) longevity. We observed that there are at least 5 transcriptional repressors of alg-1, all of which have been associated with longevity phenotypes. alg-1 knockdown delays developmental time, decreases lifespan, enhances sensitivity to sodium arsenite (NaAsO2), and inhibits longevity of glp-1(e2144) C. elegans. ALG-1 O/E, in turn, does not change its lifespan under physiological conditions or moderate heat stress; still, it increases C. elegans resistance to the oxidative stressors NaAsO2 and methyl viologen, the latter in a cel-miR-71 dependent-manner. It has also been shown that there are changes in the global pattern of miRNA expression in glp-1(e2144). Of these, a subset of miRNAs maintains differential expression in ALG-1 O/E, as well as in eat-2(ad1116), a calorie-restricted model of longevity. The present findings are indicators that ALG-1 may participate in the regulation of healthspan by acting in the defense against oxidative stressors on pathophysiological situations, and that the miRNA biogenesis pathway is a limiting factor for these effects (AU)

• FAPESP's process: 16/15958-3 - Soma-germline interaction and its effect on longevity: the role of argonautes in aging C. elegans
• Grantee: Raíssa de Paula Moro
• Support Opportunities: Scholarships in Brazil - Master