Prion Memory Potential in Plants

Prions first caught the attention of scientists when it was discovered these protein particles were responsible for infectious neurodegenerative diseases, like Mad-Cow Disease and CJD, in humans and other organismal groups.  Prions are self-perpetuating proteins with distinct functions regulated by their flexible structure (Newby & Lindquist, 2013).  Aside from the tissue degradation caused by infectious prion forms, normal prion proteins can act as “molecular memory” markers that allow for the inheritance of new traits across cell divisions (Shorter & Lindquist, 2005).  When a cell divides any changes made to the chromatin are typically erased, so prions that act as templates to save these changes enable external stimuli, like the environment, to impact the genetic information of the cell.

Memory conservation using prions has been observed in organisms from yeast to humans; however, plants were thought to record genetic changes through epigenetic marks, a method independent of prion proteins, until the work of Chakrabortee et al. (2016).  Their research aimed to identify prion-like domains (PrDs) within plant proteins and associate them with prion memory behavior.  Over 500 Arabidopsis plant proteins were identified as potential PrDs, but Chakrabortee et al. (2016) narrowed their focus to three PrDs that are involved in the flowering pathway.  Prion-like domains were identified and scored for similarity using a matching program that compared Arabidopsis protein sequences to known yeast prion sequences.  Out of the 8 proteins involved in the Arabidopsis flowering pathway, half were identified as PrDs - Luminidependens (LD), Flowering Locus PA (FPA), Flowering Locus CA (FCA), and Flowering Locus Y (FY).  Three of the Arabidopsis PrDs (LD, FPA, and PA) were expressed in yeast, and they displayed similar characteristics to yeast prions, such as foci fusion leading to one distinct foci for each protein.

Figure 1: Sup35 Assay with the flowering pathway

PrDs at low expression levels (left) and

over-expressed levels (right) on adenine-deficient 

medium. Figure taken from Chakrabortee et al. 2016.

A defining feature of prion proteins is their ability to continuously renew their structure to act as a template converting normal proteins of a similar type to the prion form.  To test this characteristic in the flowering pathway PrDs, a Sup35 protein was expressed in cells with each of the PrDs to determine if they influenced the function of this translational repressor (Sup35).  Normally Sup35 disrupts cell growth by causing the ribosomes to stop translation at the ending stop codon sequence; however, Sup35 bound to an active prion does not prevent ribosomes from reading through the stop codon to continue translation (Cai et al., 2014).  Only cells expressing the LD PrD were found to have template-like behavior, as over-expressed LD led to continued cell growth, when at lower levels of LD, Sup35 remained active and led to cell death in absence of adenine (Figure 1).  This data suggested LD PrDs have strong prion-like characteristics.

The effects of LD PrD were also observed to create heritable changes stabilized across several generations of cell growth.  Heritability is key as it allows information to be recorded and passed along from one generation to another.  The direct response of an organism to environmental changes can be retained using prion memory behavior, thus allowing faster paced phenotypic change.  With our environment changing more rapidly than ever, prions and their molecular memory may be essential for species survival (Figure 2).

Figure 2: Observed changes in flowering onset across the United States. Data from the Environmental Protection Agency marks advances and lapses in plant bloom time over two 9 year periods.  Sustained differences in bloom time may indicate the role of a heritable, molecular memory mechanism for this trait. 

The discovery of a plant protein with prion behavior is entirely new to the field of prion research.  The LD protein, which is part of the flowering pathway, clearly shows prion-like behavior in both structure and function.  The next step is to look for an association between changes in flowering patterns and LD structural changes to understand the role this PrD has in the Arabidopsis life cycle.  Plant memory mechanisms are still largely unknown, so these findings may help to explain how external stimuli can impact the chromatin in certain ways, following certain events.  This field therefore holds a great deal of potential for molecular biologists and conservation research focusing on phenotypic plant variation.

Paper:

Chakrabortee, Sohini, Can Kayatekin, Greg A. Newby, Marc L. Mendillo, Alex Lancaster, and Susan Lindquist. "Luminidependens (LD) is an Arabidopsis protein with prion behavior." Proceedings of the National Academy of Sciences (2016): 201604478. 

http://www.pnas.org/content/113/21/6065.full#ref-10

Additional Sources:

Cai, Xin, Jueqi Chen, Hui Xu, Siqi Liu, Qiu-Xing Jiang, Randal Halfmann, and Zhijian J. Chen. "Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation." Cell 156.6 (2014): 1207-1222.

Newby, Gregory A., and Susan Lindquist. "Blessings in disguise: biological benefits of prion-like mechanisms." Trends in cell biology 23.6 (2013): 251-259.

Shorter, James, and Susan Lindquist. "Prions as adaptive conduits of memory and inheritance." Nature Reviews Genetics 6.6 (2005): 435-450.

Figures:

Figure 1 - Data taken from figure 2A (Chakrabortee et al., 2016)

Figure 2 - Data from the EPA on flower bloom time - https://www.epa.gov/climate-indicators/climate-change-indicators-leaf-and-bloom-dates