(An earlier version of this post appeared at GMO Pundit blog.)
Some people have raised worries about whether novel double-stranded RNA molecules present in plant foods might be harmful to people.
Naturally occurring plants often produce novel double-stranded RNA molecules, so we have long been exposed to this potential risk.
One example of a novel plant double-stranded RNA (that was not introduced by lab genetic engineering) has been characterised in detail by Japanese scientists Makoto Kusaba and colleagues (see science reference below). It is an RNA that is present in low protein variety of rice called LGC-1 that is used as a diet therapy for patients with kidney disease.
The LGC acronym stands for Low Glutelin protein Content. Glutelin proteins are a major forms of protein storage inside rice seeds.
These Japanese scientists have analysed the fine detail of the LGC-1 mutation conferring this low-protein production in rice and discovered a mechanism that explains the low protein content of the rice. It is caused by gene silencing triggered by a plant double stranded RNA that gets generated from the mutated region of the chromosome that has been altered by the LGC mutation.
Chromosomal change causing formation of double-stranded RNA and gene-silencing.
The structure of the region of the chromosome carrying this LGC-1 mutation was shown by the Japanese scientists to be substantially reconfigured from the parental, non-mutant version by a presumably accidental spontaneous or natural radiation induced DNA rearrangement that deleted some DNA.
This DNA deletion of DNA fuses together two very similar genes called GluB4 and GluB5 (that both encode almost identical variants of the seed storage protein glutelin). Most importantly these two genes are close together on the same chromosome, but are oriented in opposite directions — pointing towards one another.
To the right is a diagram from the paper comparing chromosome structures in the region where these GluB genes reside.
The upper part which is labelled NM describes chromosome of non-mutant (parental) rice. The lower part of the diagram labelled LGC-1 describes the corresponding chromosomal structure in the low protein content mutant rice. The region present in the parental chromosome but missing in the mutated LGC-1 version of the chromosome is encircled in red in the diagram. The directions in which the genes are read by the gene transcription machinery that makes RNA message is shown by arrows.
As a result of the LGC-1 DNA deletion, the mutant chromosome carries a slightly truncated version of gene GluB5 fused to gene GluB4.
Because the GluB5 gene is oriented in the opposite direction to GlutB4 (see arrows on the diagram), in LGC-1 mutant plants, transcription of RNA starting at the GlutB4 gene and reading through GlutB5 would produce an RNA that is complementary to that normally encoding GlutB5 protein.
The consequence of this natural genetic fusion is that during gene expression that starts at the GluB4 gene in rice cells, the RNA message molecule generated from LGC-1 chromosomal segment form a molecular loop that has a regions of double-stranded RNA corresponding to the inverted highly similar genes GluB4 and GluB5.
In other words, the RNA messages for GlutB4 and the complementary RNA just mentioned for GlutB5 pair up as a double stranded RNA structure analogous to the DNA double helix.
As a result of further investigations from Kusuba and colleagues we also understand how the presence of this double-stranded RNA explains the low protein content of this rice.
The low-protein content of rice grains coming from a crop plant mutant carrying the LGC-1 gene structure arises because of a dominant genetic silencing effect of this double-stranded RNA region on all of the genes of this family of rice glutelin related genes. The double stranded RNA molecular regions trigger silencing of RNA expression from all the rice genes in this glutelin family. That’s how we get low-protein rice.
This gene family silencing example is also part of a bigger story of the biology of natural RNA silencing, and its relevance to safety assessment of plants containing novel RNA that will be explored more fully in later posts at this blog. There are several other good examples of natural gene silencing that will be described.
To appreciate the extent of natural RNA silencing, we need to bear in mind that families of multiple duplications of similar genes often occur in plant chromosomes, and analogous DNA arrangements to those that lead to gene fusion in this low protein rice LGC-1 example can easily occur when plant chromosomes of any crop in farmer’s fields are exposed to natural radiation such as cosmic rays.
Studies of crop chromosomes show that multitudinous gene rearrangements and DNA duplications have occurred in nature, so that we can be certain that novel double stranded RNAs and RNA silencing events have frequently occurred during the evolution of crop plants such as rice, maize, soy bean and wheat.
We are thus continually exposed to a natural background novel double-stranded RNA when we eat food, as this might occur when any crop variety has its chromosomes structurally shuffled by DNA damaging natural radiations.
Makoto Kusaba, Kenzo Miyahara, Shuichi Iida, Hiroyuki Fukuoka, Toshiya Takano, Hidenori Sassa, Minoru Nishimura and Takeshi Nishio
The Plant Cell June 2003 vol. 15 no. 6 1455-1467