INT272475

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Context Info
Confidence 0.61
First Reported 2008
Last Reported 2010
Negated 4
Speculated 0
Reported most in Body
Documents 15
Total Number 16
Disease Relevance 5.39
Pain Relevance 0.56

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
brain 4
skeletal muscle 3
myotube 1
heart 1
Mbnl1 (Mus musculus)
Pain Link Frequency Relevance Heat
GABAergic 100 96.36 Very High Very High Very High
imagery 112 92.20 High High
gABA 90 90.04 High High
Kinase C 5 68.80 Quite High
medulla 10 42.12 Quite Low
anesthesia 10 5.00 Very Low Very Low Very Low
interneuron 10 5.00 Very Low Very Low Very Low
Central nervous system 4 5.00 Very Low Very Low Very Low
cytokine 4 5.00 Very Low Very Low Very Low
anticonvulsant 3 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Frailty 257 99.28 Very High Very High Very High
Targeted Disruption 264 98.60 Very High Very High Very High
Spinocerebellar Ataxia Type 2 50 95.76 Very High Very High Very High
Neurological Disease 10 95.08 Very High Very High Very High
Toxicity 40 93.76 High High
Myotonic Dystrophy 58 93.04 High High
Muscle Disease 24 91.44 High High
Hypopituitarism 61 90.92 High High
Hyperinsulinism 3 88.60 High High
Disease 164 88.32 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Because CUG-BP1 and MBNL1 have been shown to be antagonistic regulators of alternative splicing of a number of different targets from work done in the myotonic dystrophy field, we reasoned that CUG-BP1 CLIP tags would be also be good candidate targets for MBNL1 regulation.
Regulation (regulation) of MBNL1 associated with frailty
1) Confidence 0.61 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.16 Pain Relevance 0
In these transgenic mice CUG-BP1 levels were found increased in skeletal muscle while no change in Mbnl1 was detected.
Neg (no) Regulation (change) of Mbnl1 in skeletal muscle associated with targeted disruption
2) Confidence 0.48 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.43 Pain Relevance 0
These data demonstrate that CUGexp transcripts dysregulate MBNL/CELF regulated pathways in the brain and provide mechanistic insight into the CNS effects of other CUGexp disorders.
Regulation (dysregulate) of MBNL in brain
3) Confidence 0.45 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719092 Disease Relevance 0.25 Pain Relevance 0.14
In addition, the antagonistic relationship between CUGBP1 and MBNL1, previously documented in heart and skeletal muscle, has not been demonstrated in the CNS.
Neg (not) Regulation (demonstrated) of MBNL1 in skeletal muscle
4) Confidence 0.45 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.09 Pain Relevance 0.09
These data provide the first evidence that CUGexp RNA gain-of-function effects in the brain involve the dysregulation of CUGBP1-MBNL1 pathways.
Regulation (dysregulation) of CUGBP1-MBNL1 in brain
5) Confidence 0.45 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.19 Pain Relevance 0.07
These data demonstrate that CUGexp transcripts dysregulate MBNL/CELF regulated pathways in the brain and provide mechanistic insight into the CNS effects of other CUGexp disorders.
Regulation (regulated) of MBNL in brain
6) Confidence 0.45 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719092 Disease Relevance 0.25 Pain Relevance 0.14
Data discussed above suggest that CUG and CCUG repeats affect MBNL1 and CUGBP1 independently through aggregated and un-aggregated CUG and CCUG repeats.
Neg (independently) Regulation (affect) of MBNL1
7) Confidence 0.37 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.27 Pain Relevance 0
CLIP was successful in identifing RNA targets of Cugbp1 but not Mbnl1.
Regulation (targets) of Mbnl1
8) Confidence 0.27 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.16 Pain Relevance 0
Expansions in coding-regions cause protein gain-of-function effects, while non-coding expansions produce toxic RNAs that alter RNA splicing activities of MBNL and CELF proteins.
Regulation (alter) of MBNL
9) Confidence 0.27 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719092 Disease Relevance 0.27 Pain Relevance 0
The discovery that CUGexp RNA and MBNL1 protein co-accumulate in ribonuclear foci in neurons suggests that, similar to the dysregulation of MBNL/CELF pathways in DM muscle, the accumulation of SCA8 CUG expansion transcripts might lead to the dysregulation of developmentally regulated splicing patterns in SCA8 brain.
Regulation (o the dysregu) of MBNL in brain associated with frailty
10) Confidence 0.27 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.24 Pain Relevance 0
In addition, CUGexp or CCUGexp transcripts accumulate as ribonuclear inclusions in DM1 and DM2 patient skeletal muscle [9]–[11] and alter the localization or regulation of RNA binding proteins CUGBP1 [12],[13] and MBNL1 [14],[15].
Regulation (regulation) of MBNL1 in skeletal muscle
11) Confidence 0.23 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 1.01 Pain Relevance 0
The DMPK transcripts containing expanded CUG repeats accumulate in nuclear foci and ultimately cause mis-splicing of secondary genes through the dysregulation of RNA-binding proteins including Muscleblind 1 (MBNL1) and CUG binding protein 1 (CUGBP1).
Regulation (dysregulation) of MBNL1
12) Confidence 0.23 Published 2010 Journal Current Chemical Genomics Section Abstract Doc Link PMC2874217 Disease Relevance 0.69 Pain Relevance 0
Best studied are the dysregulation of the splicing factors MBNL1 and CUGBP1, which either alone or in concert are sufficient to cause many of the splicing defects associated with DM1 [11, 12].
Regulation (dysregulation) of MBNL1
13) Confidence 0.23 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2874217 Disease Relevance 1.03 Pain Relevance 0
Since aberrant splicing patterns of MBNL1/CUGBP1 target genes were observed in both immortalized DM1 myoblasts and myotubes, further HTS assay development was limited to myoblasts, as this allowed for easier propagation of cells, shorter incubation times prior to luciferase readout, and was not complicated by the heterogeneity of myotube differentiation stage between wells and across experiments.
Regulation (target) of MBNL1 in myotube
14) Confidence 0.23 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2874217 Disease Relevance 0.06 Pain Relevance 0.03
A comprehensive analysis of CUGBP1-RNPs from the CUGBP1 transgenic and MBNL1-RNPs from the wild type and MBNL1 knock out mice would be one of the approaches for identification of mRNAs which are targets of CUGBP1 and MBNL1 in vivo.
Regulation (targets) of MBNL1 associated with targeted disruption
15) Confidence 0.16 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.20 Pain Relevance 0
In addition, the antagonistic relationship between CUGBP1 and MBNL1, previously documented in heart and skeletal muscle, has not been demonstrated in the CNS.
Neg (not) Regulation (demonstrated) of MBNL1 in heart
16) Confidence 0.15 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.09 Pain Relevance 0.09

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