INT255128

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Context Info
Confidence 0.37
First Reported 2008
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 13
Total Number 19
Disease Relevance 4.34
Pain Relevance 0.09

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

mRNA processing (Mbnl1) RNA binding (Mbnl1) nucleus (Mbnl1)
cytoplasm (Mbnl1)
Anatomy Link Frequency
nucleus 1
stem 1
heart 1
Mbnl1 (Mus musculus)
Pain Link Frequency Relevance Heat
anesthesia 11 89.80 High High
anticonvulsant 1 6.32 Low Low
tolerance 20 5.00 Very Low Very Low Very Low
Central nervous system 14 5.00 Very Low Very Low Very Low
cytokine 14 5.00 Very Low Very Low Very Low
imagery 14 5.00 Very Low Very Low Very Low
Kinase C 11 5.00 Very Low Very Low Very Low
GABAergic 10 5.00 Very Low Very Low Very Low
gABA 9 5.00 Very Low Very Low Very Low
spastic colon 7 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Targeted Disruption 289 95.16 Very High Very High Very High
Death 10 94.44 High High
Cv General 2 Under Development 20 93.44 High High
Toxicity 174 93.28 High High
Arrhythmias 2 Under Development 59 89.12 High High
Myotonia 98 87.04 High High
Frailty 110 86.24 High High
Heart Disease 20 84.60 Quite High
Cataract 76 84.40 Quite High
Congenital Anomalies 123 83.12 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
It seems that MBNL1 recognizes relatively short GC-rich hairpins (18 nucleotides) only if the overall RNA secondary structure is stabilized by additional sequence interactions [87].
MBNL1 Binding (recognizes) of
1) Confidence 0.37 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.17 Pain Relevance 0
Second, MBNL1 bound 70 CAG repeats in a yeast three-hybrid assay [85] whereas 162 CUG repeats readily sequestered Muscleblind but failed to induce any discernible phenotype in a Drosophila DM1 model [53].
MBNL1 Binding (bound) of
2) Confidence 0.37 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.06 Pain Relevance 0
Results from this work suggest that below a certain length threshold (<20 repeats), the A-helix structure formed by dsCUG [39] is unstable and that ssCUG are not appropriate binding targets for MBNL1.
MBNL1 Neg (not) Binding (targets) of
3) Confidence 0.37 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.18 Pain Relevance 0
Co-localization of Cy5-(CAG)10 RNA foci with MBNL1 was done by confocal microscopy (Olympus, Fluoview 1000) in 3 fluorescent channels with ?
MBNL1 Binding (foci) of
4) Confidence 0.37 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0 Pain Relevance 0
RNA recognition by MBNL proteins involves a common mechanism for both normal targets and pathogenic repeats, which implies recognition of GC-rich hairpins containing pyrimidine mismatches [87].
MBNL Binding (recognition) of
5) Confidence 0.36 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.34 Pain Relevance 0
These results demonstrate that (i) CTG tracts expressed in a context independent manner can elicit elevated Cug-bp1 levels, (ii) a two fold elevation of Cug-bp1 levels is insufficient to dysregulate splice site choice in the adult mouse heart and (iii) aggregation of Mbnl1 in CUG foci per se may not be sufficient to inactivate Mbnl1.
Mbnl1 Binding (aggregation) of in heart
6) Confidence 0.35 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.25 Pain Relevance 0.09
In these experiments both elevated Cug-bp1 levels and aggregation of Mbnl1 in intra-nuclear RNA foci are documented in conjunction with aberrant splice site selection in a set of physiologically important RNAs [24].
Mbnl1 Binding (aggregation) of
7) Confidence 0.35 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.74 Pain Relevance 0
Specifically, we have shown that siRNA mediated inactivation of MBNL1, which binds to the stem of the CUG hairpin, results in increased dispersion of nuclear foci in DM1 cells [46]. siRNA mediated reduction of hnRNP H, which binds to the base of the CUG hairpin, has also been demonstrated to allow transport of RNAs encoding expanded CUG repeats into the cytoplasm [51].
MBNL1 Binding (binds) of in stem
8) Confidence 0.33 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0 Pain Relevance 0
Thus small molecules that decrease the rate of either MBNL1 or hnRNP H binding to the mutant DMPK RNA may serve to increase its transport out of the nucleus.
MBNL1 Binding (binding) of in nucleus
9) Confidence 0.33 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0 Pain Relevance 0
Such a cadre of drugs is attractive as they may prove to be less toxic, when compared to small molecules that abolish the interaction of these proteins with the mutant DMPK RNA, as their disruptive effect on MBNL1 or hnRNP H interactions with their normal target RNAs may be less severe.


MBNL1 Binding (interactions) of
10) Confidence 0.33 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.07 Pain Relevance 0
In DM1, MBNL1 binds to and is sequestered into nuclear foci by the mutant DMPK transcripts [14, 15].
MBNL1 Binding (binds) of
11) Confidence 0.31 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2874217 Disease Relevance 0.54 Pain Relevance 0
Extensive alternative splicing in the MBNL1, 2 and 3 genes generates at least nine, three and six protein isoforms, respectively [59].
MBNL1 Binding (splicing) of
12) Confidence 0.29 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.21 Pain Relevance 0
However, recent reports found that MBNL1 binds not to only long repeats, but also to short repeats comprising of CUG as well as CAG repeats [92,93].
MBNL1 Binding (binds) of
13) Confidence 0.29 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.21 Pain Relevance 0
It has been initially suggested that MBNL1 binds exclusively to the double-stranded structures formed by long CUG repeats [31].
MBNL1 Binding (binds) of
14) Confidence 0.29 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.22 Pain Relevance 0
It seems that the best way to determine biologically relevant binding sites for these proteins is to identify mRNAs which are associated with CUGBP1 and MBNL1 in vivo, particularly in normal and in DM cells.
MBNL1 Binding (associated) of
15) Confidence 0.29 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.18 Pain Relevance 0
MBNL1 binds to the aggregated form of CUGn RNA, organized in the double-stranded helix; whereas CUGBP1 binds to the melted regions of the CUG helix [41].
MBNL1 Binding (binds) of
16) Confidence 0.21 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.12 Pain Relevance 0
The nuclear CUGn aggregates sequester MBNL1 (Muscleblind) protein [31,54], causing local reduction of MBNL1.
MBNL1 Binding (aggregates) of
17) Confidence 0.21 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.68 Pain Relevance 0
MBNL1 binds to the aggregated form of CUGn RNA, organized in the double-stranded helix; whereas CUGBP1 binds to the melted regions of the CUG helix [41].
MBNL1 Binding (binds) of
18) Confidence 0.21 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.13 Pain Relevance 0
It is interesting that CUGBP1 and MBNL1 regulate splicing of the same mRNAs (chloride channel 1, insulin receptor, troponin T) by binding to different sites [24,85].
MBNL1 Binding (binding) of
19) Confidence 0.21 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.24 Pain Relevance 0

General Comments

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