RNA-editing-mediated exon evolution

BACKGROUND: Alu retroelements are specific to primates and abundant in the human genome. Through mutations that create functional splice sites within intronic Alus, these elements can become new exons in a process denoted exonization. It was recently shown that Alu elements are also heavily changed by RNA editing in the human genome. RESULTS: Here we show that the human nuclear prelamin A recognition factor contains a primate-specific Alu-exon that exclusively depends on RNA editing for its exonization. We demonstrate that RNA editing regulates the exonization in a tissue-dependent manner, through both the creation of a functional AG 3' splice site, and alteration of functional exonic splicing enhancers within the exon. Furthermore, a premature stop codon within the Alu-exon is eliminated by an exceptionally efficient RNA editing event. The sequence surrounding this editing site is important not only for editing of that site but also for editing in other neighboring sites as well. CONCLUSION: Our results show that the abundant RNA editing of Alu sequences can be recruited as a mechanism supporting the birth of new exons in the human genome

Evidence for large diversity in the human transcriptome created by Alu RNA editing

Adenosine-to-inosine (A-to-I) RNA editing alters the original genomic content of the human transcriptome and is essential for maintenance of normal life in mammals. A-to-I editing in Alu repeats is abundant in the human genome, with many thousands of expressed Alu sequences undergoing editing. Little is known so far about the contribution of Alu editing to transcriptome complexity. Transcripts derived from a single edited Alu sequence can be edited in multiple sites, and thus could theoretically generate a large number of different transcripts. Here we explored whether the combinatorial potential nature of edited Alu sequences is actually fulfilled in the human transcriptome. We analyzed datasets of editing sites and performed an analysis of a detailed transcript set of one edited Alu sequence. We found that editing appears at many more sites than detected by earlier genomic screens. To a large extent, editing of different sites within the same transcript is only weakly correlated. Thus, rather than finding a few versions of each transcript, a large number of edited variants arise, resulting in immense transcript diversity that eclipses alternative splicing as mechanism of transcriptome diversity, although with less impact on the proteome

Imported Melioidosis, Israel, 2008

In 2008, melioidosis was diagnosed in an agricultural worker from Thailand in the southern Jordan Valley in Israel. He had newly diagnosed diabetes mellitus, fever, multiple abscesses, and osteomyelitis. Burkholderia pseudomallei was isolated from urine and blood. Four of 10 laboratory staff members exposed to the organism received chemoprophylaxis, 3 of whom had adverse events

FRET e based technique for the characterization of contour lines

a b s t r a c t Catalysts that are made of composite particles may comprise several compounds, where each compound utilizes its own specific properties, thus providing synergistic effects that cannot be found when the constituents are used separately. Developing and quality control of such particles require measuring the shape of the domains and the length of the contact line between domains made from different compounds. In what follows, the feasibility of using Fluorescence Resonance Energy Transfer (FRET) in order to gain information on the length of contour lines between neighboring domains is demonstrated. The principle of the method is to selectively adsorb the donor on one type of domain while selectively adsorbing the acceptor on the second type of domain. The requirement for a short distance between the acceptor dye molecule and the donor dye molecule in order to obtain fluorescence is then translated into a linear dependence between the emission intensity and the contour line length. This facilitates, upon using calibrated standards, the calculation of the average length of the contour between domains

Consistent levels of A-to-I RNA editing across individuals in coding sequences and non-conserved Alu repeats

Abstract Background Adenosine to inosine (A-to-I) RNA-editing is an essential post-transcriptional mechanism that occurs in numerous sites in the human transcriptome, mainly within Alu repeats. It has been shown to have consistent levels of editing across individuals in a few targets in the human brain and altered in several human pathologies. However, the variability across human individuals of editing levels in other tissues has not been studied so far. Results Here, we analyzed 32 skin samples, looking at A-to-I editing level in three genes within coding sequences and in the Alu repeats of six different genes. We observed highly consistent editing levels across different individuals as well as across tissues, not only in coding targets but, surprisingly, also in the non evolutionary conserved Alu repeats. Conclusions Our findings suggest that A-to-I RNA-editing of Alu elements is a tightly regulated process and, as such, might have been recruited in the course of primate evolution for post-transcriptional regulatory mechanisms.</p

Elevated RNA Editing Activity Is a Major Contributor to Transcriptomic Diversity in Tumors

Genomic mutations in key genes are known to drive tumorigenesis and have been the focus of much attention in recent years. However, genetic content also may change farther downstream. RNA editing alters the mRNA sequence from its genomic blueprint in a dynamic and flexible way. A few isolated cases of editing alterations in cancer have been reported previously. Here, we provide a transcriptome-wide characterization of RNA editing across hundreds of cancer samples from multiple cancer tissues, and we show that A-to-I editing and the enzymes mediating this modification are significantly altered, usually elevated, in most cancer types. Increased editing activity is found to be associated with patient survival. As is the case with somatic mutations in DNA, most of these newly introduced RNA mutations are likely passengers, but a few may serve as drivers that may be novel candidates for therapeutic and diagnostic purposes