scholarly journals The Human But Not theXenopusRNA-editing Enzyme ADAR1 Has an Atypical Nuclear Localization Signal and Displays the Characteristics of a Shuttling Protein

2001 ◽  
Vol 12 (7) ◽  
pp. 1911-1924 ◽  
Author(s):  
Christian R. Eckmann ◽  
Andrea Neunteufl ◽  
Lydia Pfaffstetter ◽  
Michael F. Jantsch
Keyword(s):  
Nuclear Localization ◽  
Nuclear Import ◽  
Rna Binding ◽  
Binding Domain ◽  
Biologically Active ◽  
Nuclear Accumulation ◽  
Dual Function ◽  
Double Stranded Rna ◽  
Rna Binding Domain ◽  
Editing Enzyme

The RNA-editing enzyme ADAR1 (adenosine deaminase that acts on RNA) is a bona fide nuclear enzyme that has been cloned from several vertebrate species. Putative nuclear localization signals (NLSs) have been identified in the aminoterminal regions of both human andXenopus ADAR1. Here we show that neither of these predicted NLSs is biologically active. Instead, we could identify a short basic region located upstream of the RNA-binding domains ofXenopus ADAR1 to be necessary and sufficient for nuclear import. In contrast, the homologous region in human ADAR1 does not display NLS activity. Instead, we could map an NLS in human ADAR1 that overlaps with its third double-stranded RNA-binding domain. Interestingly, the NLS activity displayed by this double-stranded RNA-binding domain does not depend on RNA binding, therefore showing a dual function for this domain. Furthermore, nuclear accumulation of human (hs) ADAR1 is transcription dependent and can be stimulated by LMB, an inhibitor of Crm1-dependent nuclear export, indicating that hsADAR1 can move between the nucleus and cytoplasm. Regulated nuclear import and export of hsADAR1 can provide an excellent mechanism to control nuclear concentration of this editing enzyme thereby preventing hyperediting of structured nuclear RNAs.

scholarly journals An extra double-stranded RNA binding domain confers high activity to a squid RNA editing enzyme

RNA ◽  
2009 ◽  
Vol 15 (6) ◽  
pp. 1208-1218 ◽  
Author(s):  
J. P. Palavicini ◽  
M. A. O'connell ◽  
J. J.C. Rosenthal
Keyword(s):  
High Activity ◽  
Rna Editing ◽  
Rna Binding ◽  
Binding Domain ◽  
Double Stranded Rna ◽  
Rna Binding Domain ◽  
Editing Enzyme

scholarly journals The double-stranded RNA binding domain of human Dicer functions as a nuclear localization signal

RNA ◽  
2013 ◽  
Vol 19 (9) ◽  
pp. 1238-1252 ◽  
Author(s):  
M. Doyle ◽  
L. Badertscher ◽  
L. Jaskiewicz ◽  
S. Guttinger ◽  
S. Jurado ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Rna Binding ◽  
Binding Domain ◽  
Double Stranded Rna ◽  
Localization Signal ◽  
Rna Binding Domain

scholarly journals Extra Double-stranded RNA Binding Domain (dsRBD) in a Squid RNA Editing Enzyme Confers Resistance to High Salt Environment

2012 ◽  
Vol 287 (21) ◽  
pp. 17754-17764 ◽  
Author(s):  
Juan Pablo Palavicini ◽  
Rodrigo A. Correa-Rojas ◽  
Joshua J. C. Rosenthal
Keyword(s):  
Rna Editing ◽  
Rna Binding ◽  
Binding Domain ◽  
High Salt ◽  
Double Stranded Rna ◽  
Rna Binding Domain ◽  
Editing Enzyme

scholarly journals Nucleocytoplasmic Distribution of Human RNA-editing Enzyme ADAR1 Is Modulated by Double-stranded RNA-binding Domains, a Leucine-rich Export Signal, and a Putative Dimerization Domain

2002 ◽  
Vol 13 (11) ◽  
pp. 3822-3835 ◽  
Author(s):  
Alexander Strehblow ◽  
Martina Hallegger ◽  
Michael F. Jantsch
Keyword(s):  
Rna Editing ◽  
Nuclear Localization ◽  
Nuclear Export ◽  
Rna Binding ◽  
Nuclear Export Signal ◽  
Nuclear Accumulation ◽  
Double Stranded Rna ◽  
Cytoplasmic Accumulation ◽  
Editing Enzyme ◽  
Export Signal

The human RNA-editing enzyme adenosine deaminase that acts on RNA (ADAR1) is expressed in two versions. A longer 150-kDa protein is interferon inducible and can be found both in the nucleus and cytoplasm. An amino-terminally truncated 110-kDa version, in contrast, is constitutively expressed and predominantly nuclear. In the absence of transcription, however, the shorter protein is also cytoplasmic and thus displays the hallmarks of a shuttling protein. The nuclear localization signal (NLS) of human hsADAR1 is atypical and overlaps with its third double-stranded RNA-binding domain (dsRBD). Herein, we identify regions in hsADAR1 that interfere with nuclear localization and mediate cytoplasmic accumulation. We show that interferon-inducible hsADAR1 contains a Crm1-dependent nuclear export signal in its amino terminus. Most importantly, we demonstrate that the first dsRBD of hsADAR1 interferes with nuclear localization of a reporter construct containing dsRBD3 as an active NLS. The same effect can be triggered by several other, but not all dsRBDs. Active RNA binding of either the inhibitory dsRBD1 or the NLS bearing dsRBD3 is required for cytoplasmic accumulation. Furthermore, hsADAR1's dsRBD1 has no effect on other NLSs, suggesting RNA-mediated cross talk between dsRBDs, possibly leading to masking of the NLS. A model, incorporating these findings is presented. Finally, we identify a third region located in the C terminus of hsADAR1 that also interferes with nuclear accumulation of this protein.

scholarly journals Two functionally distinct RNA-binding motifs in the regulatory domain of the protein kinase DAI.

1995 ◽  
Vol 15 (1) ◽  
pp. 358-364 ◽  
Author(s):  
S R Green ◽  
L Manche ◽  
M B Mathews
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Alpha Helix ◽  
Binding Domain ◽  
Single Amino Acid ◽  
Double Stranded Rna ◽  
C Terminus ◽  
Rna Binding Domain

The RNA-binding domain of the protein kinase DAI, the double-stranded RNA inhibitor of translation, contains two repeats of a motif that is also found in a number of other RNA-binding proteins. This motif consists of 67 amino acid residues and is predicted to contain a positively charged alpha helix at its C terminus. We have analyzed the effects of equivalent single amino acid changes in three conserved residues distributed over each copy of the motif. Mutants in the C-terminal portion of either repeat were severely defective, indicating that both copies of the motif are essential for RNA binding. Changes in the N-terminal and central parts of the motif were more debilitating if they were made in the first motif than in the second, suggesting that the first motif is the more important for RNA binding and that the second motif is structurally more flexible. When the second motif was replaced by a duplicate of the first motif, the ectopic copy retained its greater sensitivity to mutation, implying that the two motifs have distinct functions with respect to the process of RNA binding. Furthermore, the mutations have the same effect on the binding of double-stranded RNA and VA RNA, consistent with the existence of a single RNA-binding domain for both activating and inhibitory RNAs.

scholarly journals Specificity of the Double-Stranded RNA-Binding Domain from the RNA-Activated Protein Kinase PKR for Double-Stranded RNA: Insights from Thermodynamics and Small-Angle X-ray Scattering

Biochemistry ◽  
2012 ◽  
Vol 51 (46) ◽  
pp. 9312-9322 ◽  
Author(s):  
Sunita Patel ◽  
Joshua M. Blose ◽  
Joshua E. Sokoloski ◽  
Lois Pollack ◽  
Philip C. Bevilacqua
Keyword(s):  
Protein Kinase ◽  
Small Angle ◽  
Rna Binding ◽  
Binding Domain ◽  
Double Stranded Rna ◽  
X Ray ◽  
X Ray Scattering ◽  
Rna Binding Domain ◽  
Ray Scattering
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