The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs

Johnson, Rory; Guigó, Roderic

doi:10.1261/rna.044560.114

Cited by 283 publications

(283 citation statements)

References 111 publications

(172 reference statements)

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“…This is perhaps to be expected, given that mRNAs are depleted of such repeats compared to lncRNA (Kapusta et al 2013). The mechanism by which hERV prevents lncRNA from ribosomal recruitment remains to be ascertained, although we proposed recently that such fragments may interact with protein complexes that could antagonize ribosomal binding (Johnson and Guigó 2014). In summary, these findings represent a starting point for discovering features that distinguish lncRNA classes and may eventually lead to useful models for predicting such classes.…”

Section: Discussionmentioning

confidence: 78%

“…There is growing evidence that transposable elements (TEs) contribute functional sequence to lncRNA (Kelley and Rinn 2012;Johnson and Guigó 2014). Taking all TE classes together, we observed an excess of TE-derived sequence within free cytoplasmic lncRNAs compared to polysomal (0.49 mean sequence coverage versus 0.39, P = 0.05, Wilcoxon test) (Fig.…”

Section: Endogenous Retroviral Fragments Are Negatively Correlated Wimentioning

confidence: 84%

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Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells

Carlevaro-Fita

Rahim

Guigó

et al. 2016

RNA

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216

177

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Recent footprinting studies have made the surprising observation that long noncoding RNAs (lncRNAs) physically interact with ribosomes. However, these findings remain controversial, and the overall proportion of cytoplasmic lncRNAs involved is unknown. Here we make a global, absolute estimate of the cytoplasmic and ribosome-associated population of stringently filtered lncRNAs in a human cell line using polysome profiling coupled to spike-in normalized microarray analysis. Fifty-four percent of expressed lncRNAs are detected in the cytoplasm. The majority of these (70%) have >50% of their cytoplasmic copies associated with polysomal fractions. These interactions are lost upon disruption of ribosomes by puromycin. Polysomal lncRNAs are distinguished by a number of 5 ′ mRNA-like features, including capping and 5 ′ UTR length. On the other hand, nonpolysomal "free cytoplasmic" lncRNAs have more conserved promoters and a wider range of expression across cell types. Exons of polysomal lncRNAs are depleted of endogenous retroviral insertions, suggesting a role for repetitive elements in lncRNA localization. Finally, we show that blocking of ribosomal elongation results in stabilization of many associated lncRNAs. Together these findings suggest that the ribosome is the default destination for the majority of cytoplasmic long noncoding RNAs and may play a role in their degradation.

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Section: Discussionmentioning

confidence: 78%

Section: Endogenous Retroviral Fragments Are Negatively Correlated Wimentioning

confidence: 84%

Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells

Carlevaro-Fita

Rahim

Guigó

et al. 2016

RNA

Self Cite

216

177

View full text Add to dashboard Cite

show abstract

“…Similar to protein domains, it is conceivable that Alu domains have been exapted as modular functional domains in different RNA types (Gong and Maquat 2011;Johnson and Guigo 2014). The extent that Alu domains perform modular functions should become apparent soon as several research groups are investigating the function of Alu-containing RNA.…”

Section: Discussionmentioning

confidence: 99%

The domain structure and distribution of Alu elements in long noncoding RNAs and mRNAs

Kim

Wespiser

Caffrey

2015

RNA

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Approximately 75% of the human genome is transcribed and many of these spliced transcripts contain primate-specific Alu elements, the most abundant mobile element in the human genome. The majority of exonized Alu elements are located in long noncoding RNAs (lncRNAs) and the untranslated regions of mRNA, with some performing molecular functions. To further assess the potential for Alu elements to be repurposed as functional RNA domains, we investigated the distribution and evolution of Alu elements in spliced transcripts. Our analysis revealed that Alu elements are underrepresented in mRNAs and lncRNAs, suggesting that most exonized Alu elements arising in the population are rare or deleterious to RNA function. When mRNAs and lncRNAs retain exonized Alu elements, they have a clear preference for Alu dimers, left monomers, and right monomers. mRNAs often acquire Alu elements when their genes are duplicated within Alu-rich regions. In lncRNAs, reverseoriented Alu elements are significantly enriched and are not restricted to the 3 ′ and 5 ′ ends. Both lncRNAs and mRNAs primarily contain the Alu J and S subfamilies that were amplified relatively early in primate evolution. Alu J subfamilies are typically overrepresented in lncRNAs, whereas the Alu S dimer is overrepresented in mRNAs. The sequences of Alu dimers tend to be constrained in both lncRNAs and mRNAs, whereas the left and right monomers are constrained within particular Alu subfamilies and classes of RNA. Collectively, these findings suggest that Alu-containing RNAs are capable of forming stable structures and that some of these Alu domains might have novel biological functions.

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“…A frequent association of the LTRs with lncRNA transcription start sites (TSSs) suggests a role for ERVs in the evolutionary origin of lncRNAs (60). Indeed, ERV-containing lncRNAs show increased expression in ES cells relative to non-ERV lncRNA expression.…”

Section: Erv Rnas As Lncrnasmentioning

confidence: 99%

Retroviral Transcriptional Regulation and Embryonic Stem Cells: War and Peace

Schlesinger

Goff

2015

Molecular and Cellular Biology

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Retroviruses have evolved complex transcriptional enhancers and promoters that allow their replication in a wide range of tissue and cell types. Embryonic stem (ES) cells, however, characteristically suppress transcription of proviruses formed after infection by exogenous retroviruses and also of most members of the vast array of endogenous retroviruses in the genome. These cells have unusual profiles of transcribed genes and are poised to make rapid changes in those profiles upon induction of differentiation. Many of the transcription factors in ES cells control both host and retroviral genes coordinately, such that retroviral expression patterns can serve as markers of ES cell pluripotency. This overlap is not coincidental; retrovirus-derived regulatory sequences are often used to control cellular genes important for pluripotency. These sequences specify the temporal control and perhaps "noisy" control of cellular genes that direct proper cell gene expression in primitive cells and their differentiating progeny. The evidence suggests that the viral elements have been domesticated for host needs, reflecting the wide-ranging exploitation of any and all available DNA sequences in assembling regulatory networks.

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The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs

Cited by 283 publications

References 111 publications

Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells

Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells

The domain structure and distribution of Alu elements in long noncoding RNAs and mRNAs

Retroviral Transcriptional Regulation and Embryonic Stem Cells: War and Peace

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