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Alu elements as regulators of gene expression.

Häsler J, Strub K - Nucleic Acids Res. (2006)

Bottom Line: They have been shown to be involved in alternative splicing, RNA editing and translation regulation.These findings highlight how the genome adapted to these repetitive elements by assigning them important functions in regulation of gene expression.Alu elements should therefore be considered as a large reservoir of potential regulatory functions that have been actively participating in primate evolution.

View Article: PubMed Central - PubMed

Affiliation: Université de Genève, Katharina Strub, Département de Biologie Cellulaire, 30 quai Ernest Ansermet, 1211 GENEVE 4, Switzerland.

ABSTRACT
Alu elements are the most abundant repetitive elements in the human genome; they emerged 65 million years ago from a 5' to 3' fusion of the 7SL RNA gene and amplified throughout the human genome by retrotransposition to reach the present number of more than one million copies. Over the last years, several lines of evidence demonstrated that these elements modulate gene expression at the post-transcriptional level in at least three independent manners. They have been shown to be involved in alternative splicing, RNA editing and translation regulation. These findings highlight how the genome adapted to these repetitive elements by assigning them important functions in regulation of gene expression. Alu elements should therefore be considered as a large reservoir of potential regulatory functions that have been actively participating in primate evolution.

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A-to-I editing in Alu elements. (A) Deamination of adenosine by ADAR leading to the production of inosine. (B) Intramolecular base paring of a mRNA containing two Alu elements in opposite orientation. Base pairing between the two Alu elements leads to the formation of a long stable double-stranded RNA region in which ADAR performs A-to-I substitutions (marked as I).
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fig3: A-to-I editing in Alu elements. (A) Deamination of adenosine by ADAR leading to the production of inosine. (B) Intramolecular base paring of a mRNA containing two Alu elements in opposite orientation. Base pairing between the two Alu elements leads to the formation of a long stable double-stranded RNA region in which ADAR performs A-to-I substitutions (marked as I).

Mentions: RNA editing is a process by which the nucleotide sequence of RNA molecules is changed co- or post-transcriptionally. The modifications in the RNA include nucleotide insertions, deletions or base modifications. Among these modifications, base conversions appear to be the major type of editing. The best-characterized base conversions are hydrolytic deamination reactions by which cytosine are converted to uracyl and adenosine (A) to inosine (I). The A–I editing reaction is catalyzed in vivo by members of the adenosine deaminase acting on RNA (ADAR) family of enzymes (Figure 3A), which preferentially edit adenosines located in double-stranded regions of RNA molecules [for reviews see Ref. (26,27)]. The precise role of A–I editing in cell metabolism is still unclear but it has been shown that it is required for normal life; the knockout ADAR1 is embryonically lethal by liver disintegration (28), while ADAR2−/− mice die young and are prone to seizures (29). Until recently, very few positions edited by ADAR were known in the human transcriptome. This was in contrast to the apparent mass of inosine estimated to one molecule per 17 000 bases in rat brain tissue and one molecule per 33 000 bases in heart tissue (30).


Alu elements as regulators of gene expression.

Häsler J, Strub K - Nucleic Acids Res. (2006)

A-to-I editing in Alu elements. (A) Deamination of adenosine by ADAR leading to the production of inosine. (B) Intramolecular base paring of a mRNA containing two Alu elements in opposite orientation. Base pairing between the two Alu elements leads to the formation of a long stable double-stranded RNA region in which ADAR performs A-to-I substitutions (marked as I).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1636486&req=5

fig3: A-to-I editing in Alu elements. (A) Deamination of adenosine by ADAR leading to the production of inosine. (B) Intramolecular base paring of a mRNA containing two Alu elements in opposite orientation. Base pairing between the two Alu elements leads to the formation of a long stable double-stranded RNA region in which ADAR performs A-to-I substitutions (marked as I).
Mentions: RNA editing is a process by which the nucleotide sequence of RNA molecules is changed co- or post-transcriptionally. The modifications in the RNA include nucleotide insertions, deletions or base modifications. Among these modifications, base conversions appear to be the major type of editing. The best-characterized base conversions are hydrolytic deamination reactions by which cytosine are converted to uracyl and adenosine (A) to inosine (I). The A–I editing reaction is catalyzed in vivo by members of the adenosine deaminase acting on RNA (ADAR) family of enzymes (Figure 3A), which preferentially edit adenosines located in double-stranded regions of RNA molecules [for reviews see Ref. (26,27)]. The precise role of A–I editing in cell metabolism is still unclear but it has been shown that it is required for normal life; the knockout ADAR1 is embryonically lethal by liver disintegration (28), while ADAR2−/− mice die young and are prone to seizures (29). Until recently, very few positions edited by ADAR were known in the human transcriptome. This was in contrast to the apparent mass of inosine estimated to one molecule per 17 000 bases in rat brain tissue and one molecule per 33 000 bases in heart tissue (30).

Bottom Line: They have been shown to be involved in alternative splicing, RNA editing and translation regulation.These findings highlight how the genome adapted to these repetitive elements by assigning them important functions in regulation of gene expression.Alu elements should therefore be considered as a large reservoir of potential regulatory functions that have been actively participating in primate evolution.

View Article: PubMed Central - PubMed

Affiliation: Université de Genève, Katharina Strub, Département de Biologie Cellulaire, 30 quai Ernest Ansermet, 1211 GENEVE 4, Switzerland.

ABSTRACT
Alu elements are the most abundant repetitive elements in the human genome; they emerged 65 million years ago from a 5' to 3' fusion of the 7SL RNA gene and amplified throughout the human genome by retrotransposition to reach the present number of more than one million copies. Over the last years, several lines of evidence demonstrated that these elements modulate gene expression at the post-transcriptional level in at least three independent manners. They have been shown to be involved in alternative splicing, RNA editing and translation regulation. These findings highlight how the genome adapted to these repetitive elements by assigning them important functions in regulation of gene expression. Alu elements should therefore be considered as a large reservoir of potential regulatory functions that have been actively participating in primate evolution.

Show MeSH