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

Greenberger S, Levanon EY, Paz-Yaacov N, Barzilai A, Safran M, Osenberg S, Amariglio N, Rechavi G, Eisenberg E - BMC Genomics (2010)

Bottom Line: 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.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.

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Affiliation: Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel Aviv 69978, Israel.

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.

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Editing levels of specific sites in a highly-edited region of FYN is consistent among individual human skin tissues. A. Editing levels for sites in a highly-edited region of FYN are presented for 22 skin samples. Site-specific editing levels are consistent among the samples. B. Editing level and variance of the seven tested sites of FYN. Mean editing level of the seven sites ± one standard deviation.
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Figure 2: Editing levels of specific sites in a highly-edited region of FYN is consistent among individual human skin tissues. A. Editing levels for sites in a highly-edited region of FYN are presented for 22 skin samples. Site-specific editing levels are consistent among the samples. B. Editing level and variance of the seven tested sites of FYN. Mean editing level of the seven sites ± one standard deviation.

Mentions: Most editing sites in the human transcriptome occur in clusters where a number of nearby sites undergo editing. Therefore, the question arises whether editing regulation occurs at the cluster level or at the site level. That is, whether regulation is able to distinct editing sites residing in the same highly-edited region. To answer this question, we direct sequenced an Alu repeat within the last intron of the FYN gene for 32 different human skin samples and analyzed 7 different editing sites in this region (see Additional file 1). Twenty two of the samples resulted in high-quality sequence data. Distinct editing levels were found for the 7 sites (Figure 2). Mann-Whitney analysis showed the editing levels of different sites to be distinct: 20 out of 21 comparisons resulted in a significant (p < 0.05, supplementary Table 2) difference. ANOVA analysis resulted in F-ratio 68.25 (p = 4.9E-40), demonstrating that the difference in editing efficiency among various sites in the same Alu repeat is an order of magnitude larger than variability in editing efficiency of specific sites across individuals.


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

Greenberger S, Levanon EY, Paz-Yaacov N, Barzilai A, Safran M, Osenberg S, Amariglio N, Rechavi G, Eisenberg E - BMC Genomics (2010)

Editing levels of specific sites in a highly-edited region of FYN is consistent among individual human skin tissues. A. Editing levels for sites in a highly-edited region of FYN are presented for 22 skin samples. Site-specific editing levels are consistent among the samples. B. Editing level and variance of the seven tested sites of FYN. Mean editing level of the seven sites ± one standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3091749&req=5

Figure 2: Editing levels of specific sites in a highly-edited region of FYN is consistent among individual human skin tissues. A. Editing levels for sites in a highly-edited region of FYN are presented for 22 skin samples. Site-specific editing levels are consistent among the samples. B. Editing level and variance of the seven tested sites of FYN. Mean editing level of the seven sites ± one standard deviation.
Mentions: Most editing sites in the human transcriptome occur in clusters where a number of nearby sites undergo editing. Therefore, the question arises whether editing regulation occurs at the cluster level or at the site level. That is, whether regulation is able to distinct editing sites residing in the same highly-edited region. To answer this question, we direct sequenced an Alu repeat within the last intron of the FYN gene for 32 different human skin samples and analyzed 7 different editing sites in this region (see Additional file 1). Twenty two of the samples resulted in high-quality sequence data. Distinct editing levels were found for the 7 sites (Figure 2). Mann-Whitney analysis showed the editing levels of different sites to be distinct: 20 out of 21 comparisons resulted in a significant (p < 0.05, supplementary Table 2) difference. ANOVA analysis resulted in F-ratio 68.25 (p = 4.9E-40), demonstrating that the difference in editing efficiency among various sites in the same Alu repeat is an order of magnitude larger than variability in editing efficiency of specific sites across individuals.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel Aviv 69978, Israel.

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.

Show MeSH
Related in: MedlinePlus