Remodeling of the Caenorhabditis elegans non-coding RNA transcriptome by heat shock

Abstract

Elevated temperatures activate a heat shock response (HSR) to protect cells from the pathological effects of protein mis-folding, cellular mis-organization, organelle dysfunction and altered membrane fluidity. This response includes activation of the conserved transcription factor heat shock factor 1 (HSF-1), which binds heat shock elements (HSEs) in the promoters of genes induced by heat shock (HS). The upregulation of protein-coding genes (PCGs), such as heat shock proteins and cytoskeletal regulators, is critical for cellular survival during elevated temperatures. While the transcriptional response of PCGs to HS has been comprehensively analyzed in a variety of organisms, the effect of this stress on the expression of non-coding RNAs (ncRNAs) has not been systematically examined. Here we show that in Caenorhabditis elegans HS induces up- and downregulation of specific ncRNAs from multiple classes, including miRNA, piRNA, lincRNA, pseudogene and repeat elements. Moreover, some ncRNA genes appear to be direct targets of the HSR, as they contain HSF-1 bound HSEs in their promoters and their expression is regulated by this factor during HS. These results demonstrate that multiple ncRNA genes respond to HS, some as direct HSF-1 targets, providing new candidates that may contribute to organismal survival during this stress.

Three Rules Explain Transgenerational Small RNA Inheritance in C. elegans

“…These results are in agreement with the observed overlap in gene expression changes between HSF-1 High and silencer worms ( Figure 4 B, right), and HSF-1 Low and non-silencer worms ( Figure 4 B, left). Together with previous evidence showing that HSF-1 sculpts the pools of different endogenous small RNAs ( Schreiner et al., 2019 ), these observations suggest that HSF-1 can tune the function of the silencing machinery.…”

“…HSF-1 is a highly conserved transcription factor and a master regulator of proteostasis whose activity is important under stressful and non-stressful conditions ( Li et al., 2016 ). HSF-1 has been shown recently to be involved in transcriptome remodeling of non-coding RNA pools in response to heat shock in C. elegans ( Schreiner et al., 2019 ) and to account for cell-to-cell variation and phenotypic plasticity in budding yeast ( Zheng et al., 2018 ).…”

Three Rules Explain Transgenerational Small RNA Inheritance inC. elegans

“…4D ). These results, together with previous evidence that HSF-1 sculpts the pools of different endogenous small RNAs [35], suggest that HSF-1 affects multiple, separate transgenerational small RNA processes, and as such, can coordinate the broad small RNA inheritance “states”.…”

“…HSF-1 is a highly conserved transcription factor, a master regulator of proteostasis, whose activity is important under both stressful and non-stressful conditions [34]. HSF-1 was recently shown to be involved in transcriptome remodeling of non-coding RNAs’ pools in response to heat shock in C. elegans nematodes [35] and to account for cell-to-cell variation and phenotypic plasticity in budding yeast [36].…”

Diversification of the Caenorhabditis heat shock response by Helitron transposable elements

“…However, most of these studies have focused on HSF-1 binding sites that do not overlap with repetitive sequences such as transposons, potentially leaving a large gap in our understanding of the types of genes that are part of the HSR. Indeed, in previous work, we serendipitously discovered that HSF-1 promotes the expression of a full-length autonomous transposable element (TE) known as a Helitron during heat shock (Schreiner et al, 2019). Helitrons are a type of DNA transposon that are unique due to their replication and subsequent transposition occurring via a rolling-circle ‘copy-and-paste’ mechanism, which includes replication in place that results in a circular double-stranded DNA intermediate (Grabundzija et al, 2018; Kapitonov and Jurka, 2007).…”