Upstream flanking sequences and transcription of SINEs 1 1Edited by M. Gottesman

Roy, Astrid M.; West, Neva C; Rao, Aravinda; Adhikari, Prateek; Alemán, Claudina; Barnes, Anthony P.; Deininger, Prescott L.

doi:10.1006/jmbi.2000.4027

Cited by 79 publications

(54 citation statements)

References 51 publications

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“…They are heavily influenced by flanking sequences at each new insertion locus (Chesnokov and Schmid 1996;Alemán et al 2000;Roy et al 2000;Ludwig et al 2005), silenced by methylation (Englander et al 1993;Liu and Schmid 1993;Liu et al 1994), and the older Alus gradually accumulate mutations that incapacitate the internal promoter (Murphy et al 1983). Because our studies utilize an Alu whose transcription is assisted by the strong 7SL RNA gene upstream region, we cannot address the influence of genomic sequence on individual Alu loci.…”

Section: (Students Paired T-test) (C)mentioning

confidence: 99%

Diverse cis factors controlling Alu retrotransposition: What causes Alu elements to die?

Comeaux¹,

Roy-Engel²,

Hedges³

et al. 2009

Genome Res.

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The human genome contains nearly 1.1 million Alu elements comprising roughly 11% of its total DNA content. Alu elements use a copy and paste retrotransposition mechanism that can result in de novo disease insertion alleles. There are nearly 900,000 old Alu elements from subfamilies S and J that appear to be almost completely inactive, and about 200,000 from subfamily Y or younger, which include a few thousand copies of the Ya5 subfamily which makes up the majority of current activity. Given the much higher copy number of the older Alu subfamilies, it is not known why all of the active Alu elements belong to the younger subfamilies. We present a systematic analysis evaluating the observed sequence variation in the different sections of an Alu element on retrotransposition. The length of the longest number of uninterrupted adenines in the A-tail, the degree of A-tail heterogeneity, the length of the 3′ unique end after the A-tail and before the RNA polymerase III terminator, and random mutations found in the right monomer all modulate the retrotransposition efficiency. These changes occur over different evolutionary time frames. The combined impact of sequence changes in all of these regions explains why young Alus are currently causing disease through retrotransposition, and the old Alus have lost their ability to retrotranspose. We present a predictive model to evaluate the retrotransposition capability of individual Alu elements and successfully applied it to identify the first putative source element for a disease-causing Alu insertion in a patient with cystic fibrosis.

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Section: (Students Paired T-test) (C)mentioning

confidence: 99%

Diverse cis factors controlling Alu retrotransposition: What causes Alu elements to die?

Comeaux¹,

Roy-Engel²,

Hedges³

et al. 2009

Genome Res.

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“…pAluYa5-neo TET , contains a larger amount of the upstream pol III enhancer sequence of the 7SL gene (113 bp) and theAluYa5 consensus sequence from p 7SL Ya5 BC1 (Roy et al, 2000). pIRES2-EGFP (BD Biosciences Clontech) was used as the Neo R expression plasmid for toxicity control.…”

Section: Plasmidsmentioning

confidence: 99%

LINE-1 ORF1 protein enhances Alu SINE retrotransposition

Wallace

Wagstaff

Deininger

et al. 2008

Gene

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Retroelements have contributed over one third of the human genome mass. The currently active LINE-1 (L1) codes for two proteins (ORF1p and ORF2p), both strictly required for retrotransposition. In contrast, the non-coding parasitic SINE (Alu) only appears to need the L1 ORF2p for its own amplification. This requirement was previously determined using a tissue culture assay system in human cells (HeLa). Because HeLa are likely to express functional L1 proteins, it is possible that low levels of endogenous ORF1p are necessary for the observed tagged Alu mobilization. By individually expressing ORF1 and ORF2 proteins from both human (L1 RP and LRE3) and rodent (L1 A102 and L1 spa ) L1 sources, we demonstrate that increasing amounts of ORF1 expressing vector enhances tagged Alu mobilization in HeLa cells. In addition, using chicken fibroblast cells as an alternate cell culture source, we confirmed that ORF1p is not strictly required for Alu mobilization in our assay. Supporting our observations in HeLa cells, we find that tagged Alu retrotransposition is improved by supplementation of ORF1p in the cultured chicken cells. We postulate that L1 ORF1p plays either a direct or indirect role in enhancing the interaction between the Alu RNA and the required factors needed for its retrotransposition.

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“…However, these promoters are also extremely dependent on flanking sequences to stimulate expression levels in vivo (Chesnokov and Schmid 1996;Roy et al 2000b). The RNA polymerase III transcripts differ from the RNA pol II elements in that they are limited in length (generally less than 500 bases) and terminate with a short run of U's.…”

Section: Formation Of the Transcriptmentioning

confidence: 99%

Mammalian Retroelements

Deininger¹

2002

Genome Res.

352

299

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The eukaryotic genome has undergone a series of epidemics of amplification of mobile elements that have resulted in most eukaryotic genomes containing much more of this ‘junk’ DNA than actual coding DNA. The majority of these elements utilize an RNA intermediate and are termed retroelements. Most of these retroelements appear to amplify in evolutionary waves that insert in the genome and then gradually diverge. In humans, almost half of the genome is recognizably derived from retroelements, with the two elements that are currently actively amplifying, L1 and Alu, making up about 25% of the genome and contributing extensively to disease. The mechanisms of this amplification process are beginning to be understood, although there are still more questions than answers. Insertion of new retroelements may directly damage the genome, and the presence of multiple copies of these elements throughout the genome has longer-term influences on recombination events in the genome and more subtle influences on gene expression.

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Upstream flanking sequences and transcription of SINEs 1 1Edited by M. Gottesman

Cited by 79 publications

References 51 publications

Diverse cis factors controlling Alu retrotransposition: What causes Alu elements to die?

Diverse cis factors controlling Alu retrotransposition: What causes Alu elements to die?

LINE-1 ORF1 protein enhances Alu SINE retrotransposition

Mammalian Retroelements

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