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Evidence for co-evolution between human microRNAs and Alu-repeats.

Lehnert S, Van Loo P, Thilakarathne PJ, Marynen P, Verbeke G, Schuit FC - PLoS ONE (2009)

Bottom Line: The individual miRNA genes within this cluster are flanked by an Alu-LINE signature, which has been duplicated with the clustered miRNA genes.Gene duplication events in this locus are supported by comparing repeat length variations of the LINE elements within the cluster with those in the rest of the chromosome.Thus, a dual relationship exists between an evolutionary young miRNA cluster and their Alu targets that may have evolved in the same time window.

View Article: PubMed Central - PubMed

Affiliation: Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Leuven, Belgium.

ABSTRACT
This paper connects Alu repeats, the most abundant repetitive elements in the human genome and microRNAs, small RNAs that alter gene expression at the post-transcriptional level. Base-pair complementarity could be demonstrated between the seed sequence of a subset of human microRNAs and Alu repeats that are integrated parallel (sense) in mRNAs. The most common target site coincides with the evolutionary most conserved part of Alu. A primate-specific gene cluster on chromosome 19 encodes the majority of miRNAs that target the most conserved sense Alu site. The individual miRNA genes within this cluster are flanked by an Alu-LINE signature, which has been duplicated with the clustered miRNA genes. Gene duplication events in this locus are supported by comparing repeat length variations of the LINE elements within the cluster with those in the rest of the chromosome. Thus, a dual relationship exists between an evolutionary young miRNA cluster and their Alu targets that may have evolved in the same time window. One hypothesis for this dual relationship is that these miRNAs could protect against too high rates of duplicative transposition, which would destroy the genome.

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Model for dual relationship between Alu elements and miRNAs in the C19MC cluster.During the phase of rapid extension of Alu copy number, a miRNA containing cassette was duplicated from which the mature miRNA targets free (duplicating) Alu RNA. As the number of duplicated miRNA genes in the cluster grew, growth rates of Alu declined, preventing catastrophic destruction of germline genome information by Alu.
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pone-0004456-g006: Model for dual relationship between Alu elements and miRNAs in the C19MC cluster.During the phase of rapid extension of Alu copy number, a miRNA containing cassette was duplicated from which the mature miRNA targets free (duplicating) Alu RNA. As the number of duplicated miRNA genes in the cluster grew, growth rates of Alu declined, preventing catastrophic destruction of germline genome information by Alu.

Mentions: The unique design of the cluster's miRNA duplication cassette, as well as the cluster's sense Alu target capacity and the miRNA expression data were the basis to postulate a dual interaction model (Figure 6). In this model, homology sites of Alu sequences helped duplicating a gene cassette encoding miRNAs, which in turn can target sense Alu sequences and thus alter the fate of free Alu elements. This is of great interest as Alu is a retro-element that can transpose in a cycle containing a free Alu transcript, which is always in sense orientation. This model includes on one hand the fact that 3p-miRNAs of C19MC are enriched in number and production quantity and on the other hand that gene duplication events leading to growth of the cluster was facilitated by minus strand Alu repeats. Because a similar cluster is found in other primates [16], [24], which share Alu repeats with humans, it can be proposed that Alu expansion and growth of this cluster has occurred in parallel. Because many of the Alu elements within C19MC are evolutionary old (AluJ and AluS), expansion of the cluster may have occurred at an early wave of expansion of the Alu elements.


Evidence for co-evolution between human microRNAs and Alu-repeats.

Lehnert S, Van Loo P, Thilakarathne PJ, Marynen P, Verbeke G, Schuit FC - PLoS ONE (2009)

Model for dual relationship between Alu elements and miRNAs in the C19MC cluster.During the phase of rapid extension of Alu copy number, a miRNA containing cassette was duplicated from which the mature miRNA targets free (duplicating) Alu RNA. As the number of duplicated miRNA genes in the cluster grew, growth rates of Alu declined, preventing catastrophic destruction of germline genome information by Alu.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2637760&req=5

pone-0004456-g006: Model for dual relationship between Alu elements and miRNAs in the C19MC cluster.During the phase of rapid extension of Alu copy number, a miRNA containing cassette was duplicated from which the mature miRNA targets free (duplicating) Alu RNA. As the number of duplicated miRNA genes in the cluster grew, growth rates of Alu declined, preventing catastrophic destruction of germline genome information by Alu.
Mentions: The unique design of the cluster's miRNA duplication cassette, as well as the cluster's sense Alu target capacity and the miRNA expression data were the basis to postulate a dual interaction model (Figure 6). In this model, homology sites of Alu sequences helped duplicating a gene cassette encoding miRNAs, which in turn can target sense Alu sequences and thus alter the fate of free Alu elements. This is of great interest as Alu is a retro-element that can transpose in a cycle containing a free Alu transcript, which is always in sense orientation. This model includes on one hand the fact that 3p-miRNAs of C19MC are enriched in number and production quantity and on the other hand that gene duplication events leading to growth of the cluster was facilitated by minus strand Alu repeats. Because a similar cluster is found in other primates [16], [24], which share Alu repeats with humans, it can be proposed that Alu expansion and growth of this cluster has occurred in parallel. Because many of the Alu elements within C19MC are evolutionary old (AluJ and AluS), expansion of the cluster may have occurred at an early wave of expansion of the Alu elements.

Bottom Line: The individual miRNA genes within this cluster are flanked by an Alu-LINE signature, which has been duplicated with the clustered miRNA genes.Gene duplication events in this locus are supported by comparing repeat length variations of the LINE elements within the cluster with those in the rest of the chromosome.Thus, a dual relationship exists between an evolutionary young miRNA cluster and their Alu targets that may have evolved in the same time window.

View Article: PubMed Central - PubMed

Affiliation: Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Leuven, Belgium.

ABSTRACT
This paper connects Alu repeats, the most abundant repetitive elements in the human genome and microRNAs, small RNAs that alter gene expression at the post-transcriptional level. Base-pair complementarity could be demonstrated between the seed sequence of a subset of human microRNAs and Alu repeats that are integrated parallel (sense) in mRNAs. The most common target site coincides with the evolutionary most conserved part of Alu. A primate-specific gene cluster on chromosome 19 encodes the majority of miRNAs that target the most conserved sense Alu site. The individual miRNA genes within this cluster are flanked by an Alu-LINE signature, which has been duplicated with the clustered miRNA genes. Gene duplication events in this locus are supported by comparing repeat length variations of the LINE elements within the cluster with those in the rest of the chromosome. Thus, a dual relationship exists between an evolutionary young miRNA cluster and their Alu targets that may have evolved in the same time window. One hypothesis for this dual relationship is that these miRNAs could protect against too high rates of duplicative transposition, which would destroy the genome.

Show MeSH
Related in: MedlinePlus