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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.

Show MeSH
AluRNA secondary structure. Secondary structure of a Pol.III-transcribed Alu RNA drawn based on a previously determined secondary structure (34) and adapted to the sequence of the Alu element of intron 4 of the α-Fetoprotein gene (Alu Y) (69). Underlined blue letters and dots indicate the binding sites of SRP9/14 and the tertiary base pairing between the two loops, respectively, by analogy to SRP RNA (52,70).
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fig4: AluRNA secondary structure. Secondary structure of a Pol.III-transcribed Alu RNA drawn based on a previously determined secondary structure (34) and adapted to the sequence of the Alu element of intron 4 of the α-Fetoprotein gene (Alu Y) (69). Underlined blue letters and dots indicate the binding sites of SRP9/14 and the tertiary base pairing between the two loops, respectively, by analogy to SRP RNA (52,70).

Mentions: At first, the preferential editing of Alu sequences inside mRNAs might have been attributed to the secondary structure of Alu RNA that contains long double-stranded regions (34) (Figure 4). However, Athanasiadis et al. (33) determined an interesting correlation between adenosine editing inside an Alu element and the presence of an inverted Alu element in close proximity. They demonstrated that editing is favored when a distance <2 kb separates two Alu elements in opposite orientations. These data defined a model in which two closely inserted Alu elements base pair and become an ideal substrate for ADAR (Figure 3B). This model was recently confirmed by the study of the editing patterns of cyclin M3 intron 2 and NFκB1 intron 16 showing that the base pairing between two Alu elements occurs intramolecularly, and not intermolecularly (35), and therefore confirmed this model.


Alu elements as regulators of gene expression.

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

AluRNA secondary structure. Secondary structure of a Pol.III-transcribed Alu RNA drawn based on a previously determined secondary structure (34) and adapted to the sequence of the Alu element of intron 4 of the α-Fetoprotein gene (Alu Y) (69). Underlined blue letters and dots indicate the binding sites of SRP9/14 and the tertiary base pairing between the two loops, respectively, by analogy to SRP RNA (52,70).
© Copyright Policy
Related In: Results  -  Collection

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

fig4: AluRNA secondary structure. Secondary structure of a Pol.III-transcribed Alu RNA drawn based on a previously determined secondary structure (34) and adapted to the sequence of the Alu element of intron 4 of the α-Fetoprotein gene (Alu Y) (69). Underlined blue letters and dots indicate the binding sites of SRP9/14 and the tertiary base pairing between the two loops, respectively, by analogy to SRP RNA (52,70).
Mentions: At first, the preferential editing of Alu sequences inside mRNAs might have been attributed to the secondary structure of Alu RNA that contains long double-stranded regions (34) (Figure 4). However, Athanasiadis et al. (33) determined an interesting correlation between adenosine editing inside an Alu element and the presence of an inverted Alu element in close proximity. They demonstrated that editing is favored when a distance <2 kb separates two Alu elements in opposite orientations. These data defined a model in which two closely inserted Alu elements base pair and become an ideal substrate for ADAR (Figure 3B). This model was recently confirmed by the study of the editing patterns of cyclin M3 intron 2 and NFκB1 intron 16 showing that the base pairing between two Alu elements occurs intramolecularly, and not intermolecularly (35), and therefore confirmed this model.

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