cDNAs derived from primary and small cytoplasmic Alu (scAlu) transcripts

Shaikh, Tamim H.; Roy, Astrid M.; Kim, Joomyeong; Batzer, Mark A.; Deininger, Prescott L.

doi:10.1006/jmbi.1997.1161

Cited by 56 publications

(65 citation statements)

References 61 publications

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“…In addition, our data show that reverse or backward gene conversions may be more favored. It seems likely that higher levels of the Y element copy number (Shen et al 1991) or transcription (Shaikh et al 1997) may play a role in determining the directionality of the gene conversion events. Although older Alu subfamilies, such as J and Sx are present in higher copy numbers in the genome, they diverged greatly from their consensus sequences due to mutations that have accumulated throughout evolution.…”

Section: Discussionmentioning

confidence: 99%

Potential Gene Conversion and Source Genes for Recently Integrated Alu Elements

Roy¹,

Carroll²,

Nguyen³

et al. 2000

Genome Res.

108

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Alu elements comprise >10% of the human genome. We have used a computational biology approach to analyze the human genomic DNA sequence databases to determine the impact of gene conversion on the sequence diversity of recently integrated Alu elements and to identify Alu elements that were potentially retroposition competent. We analyzed 269 Alu Ya5 elements and identified 23 members of a new Alu subfamily termed Ya5a2 with an estimated copy number of 35 members, including the de novo Alu insertion in the NF1 gene. Our analysis of Alu elements containing one to four (Ya1-Ya4) of the Ya5 subfamily-specific mutations suggests that gene conversion contributed as much as 10%-20% of the variation between recently integrated Alu elements. In addition, analysis of the middle A-rich region of the different Alu Ya5 members indicates a tendency toward expansion of this region and subsequent generation of simple sequence repeats. Mining the databases for putative retroposition-competent elements that share 100% nucleotide identity to the previously reported de novo Alu insertions linked to human diseases resulted in the retrieval of 13 exact matches to the NF1 Alu repeat, three to the Alu element in BRCA2, and one to the Alu element in FGFR2 (Apert syndrome). Transient transfections of the potential source gene for the Apert's Alu with its endogenous flanking genomic sequences demonstrated the transcriptional and presumptive transpositional competency of the element.

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Section: Discussionmentioning

confidence: 99%

Potential Gene Conversion and Source Genes for Recently Integrated Alu Elements

Roy¹,

Carroll²,

Nguyen³

et al. 2000

Genome Res.

108

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“…We believe that it requires a combination of all of the factors described above to explain the relative inactivity of old Alu subfamilies and that these factors contribute differentially to silencing Alu elements at different stages of their evolution. For example, previous studies suggested about a sixfold advantage in transcription per Alu copy on average between the old and new elements (Shaikh et al 1997). If we combine this with a roughly threefold influence of subfamily mutations and a 10-fold influence of A-tail length and heterogeneity, we have the potential for 180-fold regulation.…”

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

confidence: 99%

“…It is likely that the majority of Alu elements are in relatively poor transcriptional environments that limit their activity. However, every transcriptional study carried out on Alu elements (Sinnett et al 1992;Liu et al 1994;Shaikh et al 1997) demonstrates that many Alu loci from all subfamilies continue to be transcriptionally active. Thus, the only way to explain the minimum of 4500-fold amplification preference of young Alu families, like Ya5, relative to the older Alu families is through posttranscriptional regulatory factors.…”

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

confidence: 99%

“…However, analysis of Alu transcripts recovered from cultured cells demonstrates that the majority of the transcripts (66%) were derived from the older Alu subfamilies (Sinnett et al 1992;Maraia et al 1993) and <1% derived from AluYa5 elements (Shaikh et al 1997), indicating that the RNA from older Alu elements was being made but was not undergoing retrotransposition. This expression of Alu subfamilies suggests that there is only about a sixfold difference in transcription per copy between older and younger Alus (Shaikh et al 1997). Thus, transcriptional silencing does not appear to account for the lack of activity of the older Alu elements.…”

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confidence: 99%

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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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“…the Pol III machinery [25][26][27] . While the first kind of studies give us clear evidence of transcription but are difficult to carry out on a genome-wide scale (low throughput approach), the latter ones do not provide direct evidence of transcription since the binding of the Pol III transcription machinery does not necessarily correlate with transcriptional activity [28] .…”

Section: Research Highlightmentioning

confidence: 99%

Alu expression profiles as a novel RNA signature in biology and disease

Carnevali

Dieci

2015

RNA Dis

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SINE retrotransposons of the Alu subfamily are the most numerous active mobile DNA elements in the human genome. Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, but activated in response to viral infection, genotoxic anticancer agents and other stimuli, through uncharacterized epigenetic switches interspersed throughout the genome. The elucidation of Alu RNA roles in cell biology and pathology has long been hampered by difficulties in their profiling at single-locus resolution, due to their repetitive nature. We recently found how to overcome this limitation by computational screening of RNA-seq data, thus opening the way to Alu transcriptome profiling as a novel tool to explore disease-related epigenome alterations.

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cDNAs derived from primary and small cytoplasmic Alu (scAlu) transcripts

Cited by 56 publications

References 61 publications

Potential Gene Conversion and Source Genes for Recently Integrated Alu Elements

Potential Gene Conversion and Source Genes for Recently Integrated Alu Elements

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

Alu expression profiles as a novel RNA signature in biology and disease

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