Gene silencing and control

This does not appear to be of any relevance to nutrition. I think this kind of discovery is central to the future of our science. Nutrition may play a central role in these process of control. Maybe by the usual chemicals in amino acids, proteins carbohydrates and lipids or less directly with plant secondary metbaolitres.
The discovery of RNA interference (RNAi) began a revolution in RNA biology. Previously ‘hidden’ layers of regulation of gene expression, families of small RNAs (consisting of 20-30 nucleotides) are involved in gene silencing. A diverse set of gene- regulatory mechanisms were found to use key steps in the RNAi process, including mechanisms that silence endogenous genes and mechanisms that restrain the expression of parasitic and pathogenic invaders such as transposons and viruses.
The basic RNAi process can be divided into three steps.
1. a long double-stranded RNA (dsRNA) that is expressed in, or introduced into, the cell (for example, as a result of the base-pairing of sense and antisense transcripts or the formation of stem-loop structures) is processed into small RNA duplexes by a ribonuclease III (RNaseIII) enzyme known as Dicer.
2. These duplexes are unwound, and one strand is preferentially loaded into a protein complex known as the RNA-induced silencing complex (RISC).
3. This complex effectively searches the transcriptome and finds potential target RNAs. The loaded single-stranded RNA (ssRNA), called the guide strand, then directs an endonuclease that is present in the RiSe (sometimes called the ‘slicer’ and now known to be an Argonaute protein to cleave messenger RNAs that contain sequence homologous to the ssRNA, over many rounds. In this way, the guide strand determines the sequence specificity of the RNAi response.
In different organisms, the RNAi pathways involve different proteins and mechanisms, but they operate by similar strategies. In all organisms that have been studied, RNAi involves two main components: small RNAs, which determine the specificity of the response; and Argonaute proteins, which carry out the repression. Depending on both the nature of the Argonaute in the RISC and the degree of complementarity between the small RNA and the target sequence in the mRNA, the association of the RISC with target mRNAs has been shown to have different outcomes: it can control protein synthesis and mRNA stability, maintain genome integrity or produce a specific set of small RNAs.
RNAi systems in different organisms have been refined in many ways, and such modifications include built-in molecular ‘rulers’ that define the size of small RNAs, structures that determine which strand of a small RNA is selected, mechanisms that direct further rounds of small RNA amplification, or safeguards against off-target (unrestricted and unrelated) silencing.
Siomi and Siomi 2009 On the road to reading the RNA-interference code Nature vol 457 pp 396-433
Jinek and Doudna 2009 A three dimensional view of the molecular machinery of RNA interference vol 457 pp 405-412
Moazed 2009 Small RNAs in transcriptional gene silencing and genome defence Nature vol 457 pp 413-420
Cullen 2009 Viral and cellular messenger RNA targets of viral microRNAs Nature vol 457 pp 420-425
Castanotto and Ross 2009 The promises and pitfallsof RNA-interference based therapeutics vol 457 426-433

Martin Eastwood
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