Inverted Alu dsRNA structures do not affect localization but can alter translation efficiency of human mRNAs independent of RNA editing

Capshew, Claire R.; Dusenbury, Kristen L.; Hundley, Heather A.

doi:10.1093/nar/gks590

Cited by 52 publications

(57 citation statements)

References 57 publications

(67 reference statements)

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“…The conservation of Staufen1 in C. elegans, as well as many other SMD decay factors, suggests that turnover of mRNAs having dsRNA in their 3 ′ UTRs may also occur in C. elegans. Structured 3 ′ UTRs that are hyperedited by ADAR can be sequestered in nuclear paraspeckles (Zhang and Carmichael 2001) and, when not restricted to the nucleus, have reduced translatability (Hundley et al 2008;Capshew et al 2012). One or both of these mechanisms could act upon mRNAs with EERs in their 3 ′ UTRs.…”

Section: Comparison Of Eer Data Sets With Data Sets Of Related Studiesmentioning

confidence: 99%

Genome-wide profiling of the C. elegans dsRNAome

Whipple

Youssef

Aruscavage

et al. 2015

RNA

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Recent studies hint that endogenous dsRNA plays an unexpected role in cellular signaling. However, a complete understanding of endogenous dsRNA signaling is hindered by an incomplete annotation of dsRNA-producing genes. To identify dsRNAs expressed in Caenorhabditis elegans, we developed a bioinformatics pipeline that identifies dsRNA by detecting clustered RNA editing sites, which are strictly limited to long dsRNA substrates of Adenosine Deaminases that act on RNA (ADAR). We compared two alignment algorithms for mapping both unique and repetitive reads and detected as many as 664 editing-enriched regions (EERs) indicative of dsRNA loci. EERs are visually enriched on the distal arms of autosomes and are predicted to possess strong internal secondary structures as well as sequence complementarity with other EERs, indicative of both intramolecular and intermolecular duplexes. Most EERs were associated with protein-coding genes, with ∼1.7% of all C. elegans mRNAs containing an EER, located primarily in very long introns and in annotated, as well as unannotated, 3 ′ UTRs. In addition to numerous EERs associated with coding genes, we identified a population of prospective noncoding EERs that were distant from protein-coding genes and that had little or no coding potential. Finally, subsets of EERs are differentially expressed during development as well as during starvation and infection with bacterial or fungal pathogens. By combining RNA-seq with freely available bioinformatics tools, our workflow provides an easily accessible approach for the identification of dsRNAs, and more importantly, a catalog of the C. elegans dsRNAome.

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Section: Comparison Of Eer Data Sets With Data Sets Of Related Studiesmentioning

confidence: 99%

Genome-wide profiling of the C. elegans dsRNAome

Whipple

Youssef

Aruscavage

et al. 2015

RNA

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“…6A). In addition, we identified two other components of ADARendoRNPs: Frgy2 (Ranjan et al 1993;Capshew et al 2012) and RAP55/Car-1 (Tanaka et al 2006), both of which associate with translationally repressed mRNAs in Xenopus oocytes, and the latter of which is also a component of P-bodies and stress granules in human cells (Fig. 6A).…”

Section: Adar Associates With Endogenous Xenopus Mrnasmentioning

confidence: 99%

“…Of note, this is the first report of ADAR's association with these proteins. In adult worms and human cells, ADAR does not affect the translation efficiency of RNAs containing structured 3 ′ UTRs, suggesting that ADAR's role in translational repression might be specific to early development or to X. laevis early development (Hundley et al 2008;Capshew et al 2012). An interesting question for future studies is whether all edited RNAs are incorporated into storage mRNPs in Xenopus oocytes.…”

Section: Adar-endornps: Adar-rnps Containing Endogenous Rnasmentioning

confidence: 99%

Evidence for multiple, distinct ADAR-containing complexes in Xenopus laevis

Schweidenback

Emerman

Jambhekar

et al. 2014

RNA

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ADAR (adenosine deaminase acting on RNA) is an RNA-editing enzyme present in most metazoans that converts adenosines in double-stranded RNA targets into inosines. Although the RNA targets of ADAR-mediated editing have been extensively cataloged, our understanding of the cellular function of such editing remains incomplete. We report that long, doublestranded RNA added to Xenopus laevis egg extract is incorporated into an ADAR-containing complex whose protein components resemble those of stress granules. This complex localizes to microtubules, as assayed by accumulation on meiotic spindles. We observe that the length of a double-stranded RNA influences its incorporation into the microtubule-localized complex. ADAR forms a similar complex with endogenous RNA, but the endogenous complex fails to localize to microtubules. In addition, we characterize the endogenous, ADAR-associated RNAs and discover that they are enriched for transcripts encoding transcriptional regulators, zinc-finger proteins, and components of the secretory pathway. Interestingly, association with ADAR correlates with previously reported translational repression in early embryonic development. This work demonstrates that ADAR is a component of two, distinct ribonucleoprotein complexes that contain different types of RNAs and exhibit diverse cellular localization patterns. Our findings offer new insight into the potential cellular functions of ADAR.

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“…Analysis shows that nearly 300 human genes have highly edited IRAlus in their 3′-UTRs [68], indicating that perhaps more genes are regulated by nuclear retention. Additionally, studies have shown that some mRNAs with edited 3′-UTRs are present in the cytoplasm [70,71]. It appears that several mRNAs can escape from hyper-editinginduced nuclear retention.…”

Section: Editing In Utrsmentioning

confidence: 99%

ADAR-mediated RNA editing in non-coding RNA sequences

Yang

Zhou

Jin

2013

Sci. China Life Sci.

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Adenosine to inosine (A-to-I) RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA (ADAR) proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions (UTRs) and introns are located in pre-mRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degradation, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA (miRNA), small interfering RNA (siRNA) and long non-coding RNA (lncRNA) are related to pre-mRNA splicing, translation, and gene regulation. A-to-I editing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions (UTRs and introns) and non-coding RNAs (miRNA, siRNA, and lncRNA).

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Inverted Alu dsRNA structures do not affect localization but can alter translation efficiency of human mRNAs independent of RNA editing

Cited by 52 publications

References 57 publications

Genome-wide profiling of the C. elegans dsRNAome

Genome-wide profiling of the C. elegans dsRNAome

Evidence for multiple, distinct ADAR-containing complexes in Xenopus laevis

ADAR-mediated RNA editing in non-coding RNA sequences

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