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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 1. Sites of m6A are pervasive across the genome. This shows a circos plot of all m6A peaks for humans, with HEK293T cell peaks from Meyer et al. (in red, inner circle) and HepG2 from Dominissini et al. (in blue, inner-most circle). Peaks were found in over 10,000 genes and in all chromosomes (outer sections, varying colors).
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Figure 1: Figure 1. Sites of m6A are pervasive across the genome. This shows a circos plot of all m6A peaks for humans, with HEK293T cell peaks from Meyer et al. (in red, inner circle) and HepG2 from Dominissini et al. (in blue, inner-most circle). Peaks were found in over 10,000 genes and in all chromosomes (outer sections, varying colors).

Mentions: All existing data show that m6A sites cover the majority of the genome (Fig. 1), but there is strong evidence that the sites are not randomly distributed. The enrichment of the peaks near the stop codon and 5′ end of the 3′ UTR has been replicated in both studies,2,3 and the discovered sites have exact-matching orthologous regions found in both human and mouse genes. Also, an analysis of the specific sequences that underlie the m6A sites show very high PhyloP conservation scores,2 which indicates strong evolutionary pressures at these sites. Taken together, these data indicate that m6A sites likely play a key role in the RNA biology and cellular functions of these transcripts, and that their functions are constrained over millions of years of evolution.


Novel RNA regulatory mechanisms revealed in the epitranscriptome.

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

Figure 1. Sites of m6A are pervasive across the genome. This shows a circos plot of all m6A peaks for humans, with HEK293T cell peaks from Meyer et al. (in red, inner circle) and HepG2 from Dominissini et al. (in blue, inner-most circle). Peaks were found in over 10,000 genes and in all chromosomes (outer sections, varying colors).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Figure 1. Sites of m6A are pervasive across the genome. This shows a circos plot of all m6A peaks for humans, with HEK293T cell peaks from Meyer et al. (in red, inner circle) and HepG2 from Dominissini et al. (in blue, inner-most circle). Peaks were found in over 10,000 genes and in all chromosomes (outer sections, varying colors).
Mentions: All existing data show that m6A sites cover the majority of the genome (Fig. 1), but there is strong evidence that the sites are not randomly distributed. The enrichment of the peaks near the stop codon and 5′ end of the 3′ UTR has been replicated in both studies,2,3 and the discovered sites have exact-matching orthologous regions found in both human and mouse genes. Also, an analysis of the specific sequences that underlie the m6A sites show very high PhyloP conservation scores,2 which indicates strong evolutionary pressures at these sites. Taken together, these data indicate that m6A sites likely play a key role in the RNA biology and cellular functions of these transcripts, and that their functions are constrained over millions of years of evolution.

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