Stress Resets Transgenerational Small RNA Inheritance
Preprint posted on June 13, 2019 https://www.biorxiv.org/content/10.1101/669051v1
While the concept of non-genetic, or epigenetic, inheritance is not new, there is a lack of understanding of its mechanisms and universality. Beyond the DNA sequence, small RNAs, and DNA and histone modifications (commonly methylation) embody epigenetic inheritance. Such epigenetic information was shown to alter gene expression, sometimes across generations, a phenomenon which challenges Mendelian genetics, and is termed transgenerational epigenetic inheritance. Small RNA-driven transgenerational epigenetic inheritance is a particularly prolific field of study in the nematode Caenorhabditis elegans. These tiny worms have many complex endogenous RNA interference (RNAi) pathways that employ small RNAs in silencing non-self genetic elements over generations. Moreover, C. elegans can acquire double-stranded RNA from its environment, and process it into small RNAs, which can elicit gene silencing. Both endogenous and environmental small RNAs can be inherited transgenerationally and respond to stressful stimuli, for example starvation and temperature. How small RNA inheritance is regulated is largely unknown, but now a preprint from the Rechavi lab sheds more light on these aspects using C. elegans.
- The authors performed RNAi targeting reporter transgenes, followed by exposure to three different types of stress (starvation, high temperature, and high osmolarity) in the next generation. They found that stressed worms have less reporter silencing than non-stressed worms, meaning that stress can reset ongoing environmental small RNA responses.
- Resetting of small RNA inheritance occurred both in the generation undergoing stress and in following generations.
- Stress also resets endogenous RNAi, but only in the generation undergoing stress.
- Taking advantage of the powerful C. elegans genetic toolkit, the authors determined whether RNAi resetting is altered in mutants defective for stress responses. With this approach, the authors implicated the MAPK pathway and the SKN-1 transcription factor in heritable RNAi resetting. This suggests that resetting of small RNA inheritance is downstream of conserved factors that integrate environmental stress into a physiological response.
What I like about this preprint
Previous studies have demonstrated that many C. elegans small RNA pathways cross-regulate each other, for example by competing for shared limiting factors. This work elegantly adds another dimension to this cross-regulation, and highlights the plasticity of RNAi responses to an ever-changing environment. C. elegans has a very short generation time, therefore, in the wild, RNAi resetting may enable rapid integration of new environmental signals into physiological responses. Moreover, the action of conserved stress responders upstream of RNAi resetting may be suggestive of a broadly conserved mechanism. I also like the experiments demonstrating that the resetting of RNAi is specific to stressful conditions: exposure to merely different or favorable conditions does not reset RNAi.
I find it very intriguing that endogenous RNAi, contrary to environmental RNAi, is not reset transgenerationally, indicating distinct regulation for exogenous and endogenous RNAi responses. What differentiates an exogenous response from an endogenous response within the germline? While it may be useful to recurrently integrate environmental cues, recurrently disturbing endogenous gene regulatory controls may be detrimental. Moreover, it will be interesting to determine whether MAPK genes are influencing small RNA pathways in other organisms. Or is this a nematode quirk? Indeed, worms are a great model for small RNA inheritance, a feat undoubtedly facilitated by their maternally determined germline. In mammals, wherein the germline is determined by induction, small RNA inheritance is harder to tackle.
Want to know more?
Principles of Transgenerational Small RNA Inheritance in Caenorhabditis elegans, Rechavi & Lev, 2017. https://www.sciencedirect.com/science/article/pii/S0960982217305791
Intergenerational Transmission of Gene Regulatory Information in Caenorhabditis elegans, Minkina & Hunter, 2018. https://www.sciencedirect.com/science/article/abs/pii/S0168952517301725
Intergenerational and transgenerational epigenetic inheritance in animals, Marcos Francisco Perez & Ben Lehner, 2019. https://www.nature.com/articles/s41556-018-0242-9
Posted on: 11th July 2019 , updated on: 12th July 2019Read preprint
Also in the genetics category:
CLADES: a programmable sequence of reporters for lineage analysis
|Selected by||Ying-Tsen Tung|
Species-specific oscillation periods of human and mouse segmentation clocks are due to cell autonomous differences in biochemical reaction parameters
|Selected by||Irepan Salvador-Martinez|
A conserved regulatory program drives emergence of the lateral plate mesoderm
|Selected by||Meng Zhu|
Also in the molecular biology category:
Negative Regulation of Autophagy by UBA6-BIRC6–Mediated Ubiquitination of LC3
|Selected by||Sandra Malmgren Hill|
Elucidating the molecular determinants of Aβ aggregation with deep mutational scanning
|Selected by||Suzanne McDermott|
Molecular and cellular determinants of motor asymmetry in zebrafish
|Selected by||Amrutha Swaminathan|
preListsgenetics category:in the
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
|List by||Sandra Malmgren Hill|
A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.
|List by||Shikha Nayar|
Also in the molecular biology category:
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
|List by||Rob Hynds|
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
|List by||Sandra Franco Iborra|