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Novel RNA regulatory mechanisms revealed in the epitranscriptome.

Saletore Y, Chen-Kiang S, Mason CE - RNA Biol (2013)

Bottom Line: Methyl-6-adenosine (m (6)A) has been hypothesized to exist since the 1970s, (1) but little has been known about the specific RNAs, or sites within them, that are affected by this RNA modification.Here, we report that recent work has shown RNA modifications like m (6)A, collectively called the "epitranscriptome," are a pervasive feature of mammalian cells and likely play a role in development and disease.An enrichment of m (6)A near the last CDS of thousands of genes has implicated m (6)A in transcript processing, translational regulation and potentially a mechanism for regulating miRNA maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics; Weill Cornell Medical College; New York, NY USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine; Weill Cornell Medical College; New York, NY USA; Tri-Institutional Training Program in Computational Biology and Medicine; New York, NY USA.

ABSTRACT
Methyl-6-adenosine (m (6)A) has been hypothesized to exist since the 1970s, (1) but little has been known about the specific RNAs, or sites within them, that are affected by this RNA modification. Here, we report that recent work has shown RNA modifications like m (6)A, collectively called the "epitranscriptome," are a pervasive feature of mammalian cells and likely play a role in development and disease. An enrichment of m (6)A near the last CDS of thousands of genes has implicated m (6)A in transcript processing, translational regulation and potentially a mechanism for regulating miRNA maturation. Also, because the sites of m (6)A show strong evolutionary conservation and have been replicated in nearly identical sites between mouse and human, strong evolutionary pressures are likely being maintained for this mark. (2)(,) (3) Finally, we note that m (6)A is one of over 100 modifications of RNA that have been reported, (4) and with the combination of high-throughput, next-generation sequencing (NGS) techniques, immunoprecipitation with appropriate antibodies and splicing-aware peak-finding, the dynamics of the epitranscriptome can now be mapped and characterized to discern their specific cellular roles.

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Figure 2. Effects of m6A on RNA function. We hypothesize that the sites of m6A (blue) will prevent the N-6 de-amination that occurs in RNA editing (red), where adenosine (A) gets converted into inosine (I) then guanosine (G). These sites may then have many roles in the function of RNA, from splicing to translation changes (blue).
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Figure 2: Figure 2. Effects of m6A on RNA function. We hypothesize that the sites of m6A (blue) will prevent the N-6 de-amination that occurs in RNA editing (red), where adenosine (A) gets converted into inosine (I) then guanosine (G). These sites may then have many roles in the function of RNA, from splicing to translation changes (blue).

Mentions: Another potential regulatory role for m6A is in the post-transcriptional modification of A→I editing, which results from the deamination of the N6 in adenosine by the ADAR family of adenosine deaminases. Intriguingly, m6A is known to block the activity of the ADAR enzymes that perform A→I conversion in mRNA.27 Inosine is treated as guanosine in translation and when forming RNA secondary structures,28 so m6A may serve as a mechanism to maintain adenosines in transcripts and hinder RNA editing. However, the challenge is both in finding existing A→I editing sites and seeing a dynamic change induced by an introduction of an m6A site. So far, there is no m6A peak that overlaps with any known RNA editing site, which gives some support for this hypothesis (Fig. 2).


Novel RNA regulatory mechanisms revealed in the epitranscriptome.

Saletore Y, Chen-Kiang S, Mason CE - RNA Biol (2013)

Figure 2. Effects of m6A on RNA function. We hypothesize that the sites of m6A (blue) will prevent the N-6 de-amination that occurs in RNA editing (red), where adenosine (A) gets converted into inosine (I) then guanosine (G). These sites may then have many roles in the function of RNA, from splicing to translation changes (blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672275&req=5

Figure 2: Figure 2. Effects of m6A on RNA function. We hypothesize that the sites of m6A (blue) will prevent the N-6 de-amination that occurs in RNA editing (red), where adenosine (A) gets converted into inosine (I) then guanosine (G). These sites may then have many roles in the function of RNA, from splicing to translation changes (blue).
Mentions: Another potential regulatory role for m6A is in the post-transcriptional modification of A→I editing, which results from the deamination of the N6 in adenosine by the ADAR family of adenosine deaminases. Intriguingly, m6A is known to block the activity of the ADAR enzymes that perform A→I conversion in mRNA.27 Inosine is treated as guanosine in translation and when forming RNA secondary structures,28 so m6A may serve as a mechanism to maintain adenosines in transcripts and hinder RNA editing. However, the challenge is both in finding existing A→I editing sites and seeing a dynamic change induced by an introduction of an m6A site. So far, there is no m6A peak that overlaps with any known RNA editing site, which gives some support for this hypothesis (Fig. 2).

Bottom Line: Methyl-6-adenosine (m (6)A) has been hypothesized to exist since the 1970s, (1) but little has been known about the specific RNAs, or sites within them, that are affected by this RNA modification.Here, we report that recent work has shown RNA modifications like m (6)A, collectively called the "epitranscriptome," are a pervasive feature of mammalian cells and likely play a role in development and disease.An enrichment of m (6)A near the last CDS of thousands of genes has implicated m (6)A in transcript processing, translational regulation and potentially a mechanism for regulating miRNA maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics; Weill Cornell Medical College; New York, NY USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine; Weill Cornell Medical College; New York, NY USA; Tri-Institutional Training Program in Computational Biology and Medicine; New York, NY USA.

ABSTRACT
Methyl-6-adenosine (m (6)A) has been hypothesized to exist since the 1970s, (1) but little has been known about the specific RNAs, or sites within them, that are affected by this RNA modification. Here, we report that recent work has shown RNA modifications like m (6)A, collectively called the "epitranscriptome," are a pervasive feature of mammalian cells and likely play a role in development and disease. An enrichment of m (6)A near the last CDS of thousands of genes has implicated m (6)A in transcript processing, translational regulation and potentially a mechanism for regulating miRNA maturation. Also, because the sites of m (6)A show strong evolutionary conservation and have been replicated in nearly identical sites between mouse and human, strong evolutionary pressures are likely being maintained for this mark. (2)(,) (3) Finally, we note that m (6)A is one of over 100 modifications of RNA that have been reported, (4) and with the combination of high-throughput, next-generation sequencing (NGS) techniques, immunoprecipitation with appropriate antibodies and splicing-aware peak-finding, the dynamics of the epitranscriptome can now be mapped and characterized to discern their specific cellular roles.

Show MeSH