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A dual purpose RNA and Hox regulation. A new paper in Plos Genetics shows that a long non-coding RNA regulates the expression of a Hox gene in Drosophila in cis.

A dual purpose RNA and Hox regulation

This finding suggests an explanation for the co-linearity displayed by Hox genes between genomic arrangement and expression pattern. The Ultrabithorax mutant. Hox genes are master-regulators of positional identity along the anterior-posterior axis throughout bilaterian animals. Hox genes are found in genomic clusters in which their 3′-5′ organisation mirrors their expression pattern along the A-P axis. This correspondence between body axis and genomic organisation is termed co-linearity. The Hox gene cluster is actually divided into two partial clusters in Drosophila; the Antennapedia complex (ANT-C) and the Bithorax complex (BX-C). Figure showing the expression of ABD-A (red), and ABD-B (green) in the embryonic CNS.

Abd-A is expressed in the embryonic epidermis and CNS in parasegments (PS) 7-12 but is excluded from PS13. Like this: Like Loading... Double-strand break interacting RNAs (diRNAs) A new role for small RNAs in the repair of DNA double-strand breaks has been reported in Cell.

Double-strand break interacting RNAs (diRNAs)

Wei et al. have found diRNAs, derived from the vicinity of DNA double-strand breaks, in both Arabidopsis thaliana and human cells. DNA double strand breaks (DSBs) are a particularly deleterious form of DNA damage as they can cause chromosomal translocations and induce cell death. To maintain the genome’s integrity, eukaryotic cells employ two different mechanisms of DSB repair. Non-homologous end joining (NHEJ) is an efficient mechanism that rapidly repairs DSBs without requiring an homologous template.

However, NHEJ often causes insertions or deletions at the break site. Wei et al. used an assay system that monitors DSB repair by SSA in the model plant Arabidopsis thaliana. The first clue that suggested that small RNAs may be involved in double strand break repair came when they crossed their DSB repair assay system into lines mutant for Dicer-like proteins (DCL). Like this: Like Loading... Small silencing RNAs. I: Piwi-interacting RNAs. Three major classes of small RNAs involved in gene silencing have been found in animals: microRNAs (miRNAs), small-interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). miRNAs are involved in the regulation of mRNA stability and translation, whilst the main purpose of the siRNA and piRNA pathways appears to be the defense of the cell and genome from viruses and transposable elements.

small silencing RNAs. I: Piwi-interacting RNAs.

Unlike the other two systems that are ubiquitously active, the piRNA pathway is generally only active in germline cells, the most important locus of defense against transposons. A common feature of all three pathways is the formation of RNA-induced silencing complexes (RISCs), composed of a small RNA bound to an Argonaute family protein. The small RNA guides RISC to specific target RNAs, resulting in target silencing (generally by the Argonaute protein ‘slicing’ the cognate RNA).

The piRNA system in Drosophila A Drosophila melanogaster egg chamber. The piRNA pathway in somatic follicle cells. RNAi and Chromatin Modification. RNAi silences genes by targeting mRNAs for degradation.

RNAi and Chromatin Modification

However, a second mode by which RNAi effects gene silencing has emerged: by triggering chromatin modifications. Gu et al have analysed the pattern of a specific chromatin modification in response to exogenous double stranded RNA (dsRNA) in C. elegans and show that RNAi triggered chromatin modification is target gene specific and transgenerationally heritable. The ability of exogenous dsRNAs to silence homologous target genes (RNA interference, RNAi) was discovered in the nematode worm, C. elegans, approximately fifteen years ago. Feeding worms bacteria expressing dsRNA, or bathing worms in dsRNA, has the ability to specifically block gene function and most surprisingly this effect in C. elegans is inherited for some generations.

RNAi has become an incredibly useful technique in biology as it works to a greater or lesser extent throughout eukarya, and offers a simple and fast method for compromising gene action specifically.