Micropeptides

Complementary Peptides (cPEPs): A Novel Micropeptide Technology for Crop Protection

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Our new study published in Nature Communications describes the discovery of a novel peptide-based approach for modulating protein expression in plants.  

A major challenge in agriculture today is maintaining food production in the face of multiple threats that are reducing crop yields, including climate change, limited access to fertilizers, and the need to reduce chemical pesticides and herbicides to minimize environmental and public health risks. Farmers are losing crop protection tools faster than they are being replaced, and urgently need new natural and safe solutions.  

We recently published the discovery of a novel class of short peptides that could solve this problem. The study appears in Nature Communications in an article entitled “Complementary Peptides Represent a Credible Alternative to Agrochemicals by Activating Translation of Targeted Proteins.” In our study, we reported the promising discovery of a new class of small proteins in plants called complementary peptides (cPEPs). cPEPS are short peptides that increase the abundance of the targeted protein by enhancing translation. Thus, treating plants with cPEPs targeting proteins involved in different biological processes could improve the growth of plants or increase their resistance to various stresses. 

cPEPs for Crop Protection and Beyond 

We first discovered cPEPS while characterizing short peptides produced by plants that physically interact with their nascent mRNA sequences.  We found that they are short protein sequences derived from RNA code within a parent gene. We demonstrated that cPEPs could interact with ribosomes to increase the translation of mRNA coding for the parent protein. As such, they may offer a simple way to modify protein expression directly.  

In our study, we found that watering and spraying plants with synthetic cPEPs targeting various proteins produced agronomic benefits in common crops. For example, treatment with cPEPs targeting the JAR1 protein improved the resistance of tomatoes to a pathogenic fungus. In contrast, treatment with cPEPs targeting the proteins SHY2, MRB1, and SGR1 promoted the development of soybeans in the absence of fertilizers. Moreover, treatment of cPEPs targeting HSP101 enhanced the resistance of soybeans to heat stress 

Beyond utilization in agriculture, cPEPs could have exciting implications for basic research. Since cPEPs could directly modify the expression of plant proteins, scientists may readily utilize them to uncover the role of unknown plant genes. More broadly, cPEPs are one new component of an untapped research frontier, including microRNAs, miPEPs, and other small regulatory factors. By learning more about how these factors function, we may better understand the complicated mechanisms by which gene expression is regulated, leading to specific phenotypes in organisms.  

Thinking Ahead 

Our initial results raise exciting possibilities. Firstly, many technologies today, such as GMOs and CRISPR, permanently modify the genome, restricting the plant’s ability to respond if growing conditions change in any way. In contrast, cPEPs like miPEPs, only temporarily alter plant biology after treatment by watering or spraying.  

Micropep has based its current pipeline on over a decade of research on miPEPs: short peptides that amplify the production of their parent microRNA. While our cPEP research is comparatively new, if the science holds, it could represent a second biological phenomenon for us to leverage to generate practical, easy-to-use products for promoting crop protection. Such a possibility is attractive because, in practice, miPEPs and cPEPs have different characteristics that are advantageous in different situations.   

For example, miPEPs are not generally evolutionarily conserved across species. Whenever we want to modulate some aspect of a plant species, we must create a different miPEP for the job. This quality is valuable when we want to make a product that only affects one plant type. On the other hand, the cPEP system may offer more flexibility. We could generate cPEPs that are either well-conserved or species-specific, depending on what kind of product we want to make. Thus, we could fine-tune the selectivity of our crop protection products from addressing a single specific use case to targeting multiple species with a single broad-spectrum cPEP.  

By using both the miPEP and cPEP systems to generate new product candidates, we may one day be able to expand the range of crop protection benefits that our products offer. But for now, we’re excited by all the potential that cPEPs represent, and we look forward to continuing to explore the rules that govern what constitutes an optimal cPEP and the capabilities and limitations of this system.  

Through our work, we aim to leverage scientific breakthroughs like these to deliver much-needed sustainable products to the market in order to help farmers overcome the challenges they face every day.  

Read the study to learn more.