RNA aptamers binding the double-stranded RNA-binding domain

Hallegger, Martina; Taschner, Andreas; Jantsch, Michael F.

doi:10.1261/rna.125506

Cited by 23 publications

(49 citation statements)

References 38 publications

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“…This is consistent with the Staufen-binding site in the Drosophila bicoid mRNA that included three stem-loops (Ferrandon et al 1994). Similarly, other dsRNA-binding proteins were shown to bind complex RNA structures composed of stems, bulges, and loops (Herbert and Rich 2001;Hallegger et al 2006). The nature of the Stau2-binding site is completely unknown.…”

Section: Staufen-binding Sitesupporting

confidence: 65%

A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes

Furic¹,

Maher-Laporte²,

DesGroseillers³

2007

RNA

114

120

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Messenger RNAs are associated with multiple RNA-binding proteins to form ribonucleoprotein (mRNP) complexes. These proteins are important regulators of the fate of their target mRNAs. In human cells, Staufen1 and Staufen2 proteins, coded by two different genes, are double-stranded RNA-binding proteins involved in several cellular functions including mRNA localization, translation, and decay. Although 51% identical, these proteins are nevertheless found in different RNA particles. In addition, differential splicing events generate Staufen2 isoforms that only differ at their N-terminal extremities. In this paper, we used a genome-wide approach to identify and compare the mRNA targets of mammalian Staufen proteins. The mRNA content of Staufen mRNPs was identified by probing DNA microarrays with probes derived from mRNAs isolated from immunopurified Staufen-containing complexes following transfection of HEK293T cells with Stau1 55 -HA, Stau2 59 -HA, or Stau2 62 -HA expressors. Our results indicate that 7% and 11% of the cellular RNAs expressed in HEK293T cells are found in Stau1-and in Stau2-containing mRNPs, respectively. A comparison of Stau1-and Stau2-containing mRNAs identifies a relatively low percentage of common mRNAs; the percentage of common mRNAs highly increases when mRNAs in Stau2 59 -HA-and Stau2 62 -containing mRNPs are compared. There is a predominance of mRNAs involved in cell metabolism, transport, transcription, regulation of cell processes, and catalytic activity. All these subsets of mRNAs are mostly distinct from those associated with FMRP or IMP, although some mRNAs overlap. Consistent with a model of post-transcriptionnal gene regulation, our results show that Stau1-and Stau2-mRNPs associate with distinct but overlapping sets of cellular mRNAs.

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Section: Staufen-binding Sitesupporting

confidence: 65%

A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes

Furic¹,

Maher-Laporte²,

DesGroseillers³

2007

RNA

114

120

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“…38,39 In long, almost completely doublestranded RNA ADAR activity converts several if not most adenosines to inosines. 40 On the other hand, in site selective editing only a few adenosines are deaminated within an imperfect RNA stem loop structure.…”

Section: The Adar Enzyme Familymentioning

confidence: 99%

Proteome diversification by adenosine to inosine RNA-editing

Pullirsch

Jantsch²

2010

RNA Biology

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“…Evidence suggests that dsRBDs consisting of 65-70 amino acids provide general binding with little sequence selectivity, although the number and distance between dsRBDs may provide some specificity for its substrates and recognize distinct structural determinants within dsRNA (27,(33)(34)(35). Two reported dsRBD structures for Xenopus laevis RNA-binding protein A (Xlrbpa) and the Drosophila Staufen protein interacting with dsRNA reveal that the domain makes important contacts across the major groove of a dsRNA helix (36, 37).…”

Section: Rna Editing Mediated By Adenosine Deaminases Acting On Rna (mentioning

confidence: 99%

RNA Binding-independent Dimerization of Adenosine Deaminases Acting on RNA and Dominant Negative Effects of Nonfunctional Subunits on Dimer Functions

Valente

Nishikura

2007

Journal of Biological Chemistry

125

114

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RNA editing that converts adenosine to inosine in doublestranded RNA (dsRNA) is mediated by adenosine deaminases acting on RNA (ADAR). ADAR1 and ADAR2 form respective homodimers, and this association is essential for their enzymatic activities. In this investigation, we set out experiments aiming to determine whether formation of the homodimer complex is mediated by an amino acid interface made through protein-protein interactions of two monomers or via binding of the two subunits to a dsRNA substrate. Point mutations were created in the dsRNA binding domains (dsRBDs) that abolished all RNA binding, as tested for two classes of ADAR ligands, long and short dsRNA. The mutant ADAR dimer complexes were intact, as demonstrated by their ability to co-purify in a sequential affinity-tagged purification and also by their elution at the dimeric fraction position on a size fractionation column. Our results demonstrated ADAR dimerization independent of their binding to dsRNA, establishing the importance of protein-protein interactions for dimer formation. As expected, these mutant ADARs could no longer perform their catalytic function due to the loss in substrate binding. Surprisingly, a chimeric dimer consisting of one RNA binding mutant monomer and a wild type partner still abolished its ability to bind and edit its substrate, indicating that ADAR dimers require two subunits with functional dsRBDs for binding to a dsRNA substrate and then for editing activity to occur. RNA editing mediated by adenosine deaminases acting on RNA (ADAR)2 involves adenosine-to-inosine (A 3 I) changes in double-stranded RNA (dsRNA) (1-4). A 3 I RNA editing can alter the protein coding sequence of several genes to create various isoforms, such as in the glutamate receptor ion channel subunits (5, 6), serotonin 2C subtype receptors (7), and Kv1.1 potassium channel (8). The association of malfunctioning A 3 I editing mechanisms and certain human disease, such as neurodegeneration in amyotrophic lateral sclerosis and depression in suicide victims has been implicated (9, 10). Bioinformatic approaches have revealed numerous A 3 I editing sites within non-coding sequences in introns and untranslated regions harboring repetitive elements such as . Furthermore, recent evidence has revealed the intersection of ADAR with the RNA interference pathway, indicating a much broader role for A 3 I RNA editing (16 -21). A 3 I RNA editing is mediated by ADAR (1-4). In vertebrates, three separate ADAR family members have been identified, and they are conserved in their C-terminal deaminase region as well as in their N-terminal double-stranded RNA binding domains (dsRBDs) (22)(23)(24)(25)(26)(27)(28)(29). ADARs are also present in invertebrates, such as a single Drosophila member (dADAR) that is similar to the mammalian ADAR2 (30), as well as two less conserved Caenorhabditis elegans members (c.e.ADR1 and c.e.ADR2) (22, 31).The common structural features shared by mammalian ADARs include dsRBDs repeated two or three times that are located in the N-terminal region...

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RNA aptamers binding the double-stranded RNA-binding domain

Cited by 23 publications

References 38 publications

A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes

A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes

Proteome diversification by adenosine to inosine RNA-editing

RNA Binding-independent Dimerization of Adenosine Deaminases Acting on RNA and Dominant Negative Effects of Nonfunctional Subunits on Dimer Functions

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