A genetic screen identifies C. elegans eif-3.H and hrpr-1 as pro-apoptotic genes and potential activators of egl-1 expression

TL;DR

The study identifies two genes in C. elegans that help control cell death by influencing the expression of a key apoptosis gene.

Contribution

The paper discovers eif-3.H and hrpr-1 as novel pro-apoptotic genes that activate egl-1 expression in C. elegans.

Findings

Knockdown of eif-3.H or hrpr-1 leads to survival of unwanted cells during C. elegans development.

eif-3.H and hrpr-1 are potential activators of egl-1 expression.

egl-1 is regulated at both transcriptional and post-transcriptional levels.

Abstract

During
C. elegans
development, 1090 somatic cells are generated of which 131 reproducibly die, many through apoptosis. The
C. elegans
BH3-only gene

egl-1

is the key activator of apoptosis in somatic tissues, and it is predominantly expressed in ‘cell death' lineages i.e. lineages in which apoptotic cell death occurs.

egl-1

expression is regulated at the transcriptional and post-transcriptional level. For example, we previously showed that the miR-35 and miR-58 families of miRNAs repress

egl-1

expression in mothers of ‘unwanted' cells by binding to the 3′ UTR
of

egl-1

mRNA, thereby increasing

egl-1

mRNA turnover. In a screen for RNA-binding proteins with a role in the post-transcriptional control of

egl-1

expression, we identified
EIF-3.H
(ortholog of human eIF3H) and
HRPR-1
(ortholog human hnRNP R/Q) as potential activators of

egl-1

expression. In addition, we demonstrate that the knockdown of the

eif-3.H

or

hrpr-1

gene by RNA-mediated interference (RNAi) results in the inappropriate survival of unwanted cells during
C. elegans
development. Our study provides novel insight into how

egl-1

expression is controlled to cause the reproducible pattern of cell death observed during
C. elegans
development.

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