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Hope Not Hype - Third World Network

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Appendix One: What is a GMO<br />

135<br />

Once these conditions are met, then gene silencing results from “the cleavage or<br />

translational repression of complementary single-stranded RNAs, such as messenger RNAs<br />

or viral genomic/antigenomic RNAs. The short RNAs have also been implicated in guiding<br />

chromatin modification”, DNA methylation, or histone modifications, the latter of which<br />

are heritable by separate pathways (see also Chong and Whitelaw, 2004; Lippman and<br />

Martienssen, 2004; quote from Meister and Tuschl, 2004, p. 343).<br />

The classification of RNAi/PTGS as an epigenetic [heritable] phenomenon rests largely<br />

upon its ability to provoke heritable changes in gene expression. Inheritance of silencing<br />

could derive from either of two sources. The first is persistence of the signal. The second is<br />

persistence of the silenced state (Bernstein et al., 2001, p. 1516).<br />

When dsRNA is a signal that is maintained through sequence-specific degradation<br />

and/or RNA-dependent RNA polymerase (RdRP) amplification (Mello and Conte Jr., 2004),<br />

the trait is dependent on propagation of the signal (e.g., dsRNA). One way for this to<br />

occur is through “stable incorporation of transgene arrays into the genome, the presence<br />

of endogenous repetitive elements such as transposons, or the enforced expression of<br />

hairpin RNAs. Such cases require no additional mechanisms to explain heritable silencing<br />

because the trigger is expressed from an endogenous and heritable genetic element”<br />

(Bernstein et al., 2001, p. 1516). By “heritable genetic element” these authors mean DNA,<br />

a case already recognized by ERMA. “The latter case is more provocative and requires<br />

consideration of mechanisms that propagate either the signal or the silenced state<br />

independently of the silencing trigger” (Bernstein et al., 2001, p. 1516). This is the case I<br />

argue should also be recognized by ERMA as a GMO under the existing wording of the<br />

Act.<br />

Numerous types of instigating events lead to gene silencing, including: in vitro<br />

synthesized dsRNA, a novel mRNA precursor (as could arise from a transgene, a new<br />

open reading frame resulting from a DNA insertion, or a new intron), or a product of<br />

transcription expressed in a cell type or time of development where it would not normally<br />

occur, as could happen if a transgene activated a region of heterochromatic DNA (Denli<br />

and Hannon, 2003; Grewal and Elgin, 2007). New dsRNAs could arise when endogenous<br />

RNA editing pathways act on a foreign RNA substrate (Heinemann and Bungard, 2005;<br />

Yang et al., 2006). Finally, novel dsRNAs may be created in one organism and transferred<br />

through food to, and amplified in, another organism (Baum et al., 2007; Mao et al., 2007).<br />

The initiating event can require nothing more than common promoters or other types<br />

of DNA-level regulatory elements on two different genes or any “aberrant RNA” (Al-<br />

Kaff et al., 2000; Bhullar et al., 2003; Heinemann, 2007; Herr et al., 2006). Thus, a new<br />

form of dsRNA can arise when two different transgenes run by common promoters combine<br />

through breeding in the open environment, or when a virus, such as the CaMV, that carries<br />

the original promoter for a transgene, for example the 35S promoter 4 , infects a transgenic<br />

plant.<br />

4<br />

Currently the most commonly used promoter in GM crops.

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