INT159519

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Context Info
Confidence 0.64
First Reported 2008
Last Reported 2009
Negated 1
Speculated 0
Reported most in Body
Documents 2
Total Number 23
Disease Relevance 4.96
Pain Relevance 0.64

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 (Smn1) nucleolus (Smn1) RNA binding (Smn1)
nucleus (Smn1) cytoplasm (Smn1)
Anatomy Link Frequency
tail 2
fibroblasts 2
central nervous system 2
motor neuron 1
Smn1 (Mus musculus)
Pain Link Frequency Relevance Heat
Migraine 1 99.44 Very High Very High Very High
Central nervous system 44 98.60 Very High Very High Very High
Intracerebroventricular 44 96.44 Very High Very High Very High
Spinal cord 88 80.60 Quite High
fibrosis 22 7.40 Low Low
anesthesia 22 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Spinal Muscular Atrophy 711 99.48 Very High Very High Very High
Headache 1 99.44 Very High Very High Very High
Epilepsy 1 99.18 Very High Very High Very High
Disease 134 98.64 Very High Very High Very High
Death 23 85.16 High High
Aging 22 74.28 Quite High
Targeted Disruption 22 73.84 Quite High
Neurodegenerative Disease 22 31.84 Quite Low
Frailty 22 12.64 Low Low
Epidermolysis Bullosa Simplex 22 11.68 Low Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The pMU3 vector was also capable of re-directing endogenous SMN pre-mRNA splicing in primary SMA fibroblasts, resulting in approximately a three-fold increase over pM13 levels of trans-splicing and a comparable increase in steady state levels of SMN protein (Figure 4B).


Positive_regulation (increase) of SMN in fibroblasts associated with spinal muscular atrophy
1) Confidence 0.64 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.10 Pain Relevance 0
Western blots were repeated in quadruplicate to confirm 2-tail t-test statistical significance of the increase in SMN protein.
Positive_regulation (increase) of SMN in tail
2) Confidence 0.64 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0 Pain Relevance 0
In the absence of an intact acceptor site at the intron 7/exon 8 junction, SMN trans-splicing was again elevated several fold over the standard SMN2 mini-gene (Figure 1C).
Positive_regulation (elevated) of SMN
3) Confidence 0.64 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0 Pain Relevance 0
SMN protein induction was measured using pIn711 ASO as baseline, and fold change over pM13 alone (triplicate mean set to 1) as expressions of trans-splicing efficiency.


Positive_regulation (induction) of SMN
4) Confidence 0.64 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0 Pain Relevance 0
These results demonstrate that endogenous SMN transcripts can be re-directed by trans-splicing and that SMN levels can be significantly increased by the ASO/trans-splicing strategy in a relevant disease context.


Positive_regulation (increased) of SMN associated with disease
5) Confidence 0.64 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.30 Pain Relevance 0
Consistent with the U1 results, pMU3 treated extracts were able to significantly elevate functional SMN levels as measured by U11ATACsnRNP assembly.
Positive_regulation (elevate) of SMN
6) Confidence 0.55 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.07 Pain Relevance 0
To normalize within experiments, trans-SMN induction is determined as (trans-SMN:GAPDH) and between experiments levels were normalized to basal pM13 trans-splicing values (set to 1).
Positive_regulation (induction) of trans-SMN
7) Confidence 0.55 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.08 Pain Relevance 0
Gems have proven a valuable tool to monitor the efficiency of SMN induction from a variety of therapeutic molecules, ranging from drugs to viral vectors.
Positive_regulation (induction) of SMN
8) Confidence 0.55 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.10 Pain Relevance 0
To normalize within experiments, SMN induction is determined as (SMN:?
Positive_regulation (induction) of SMN
9) Confidence 0.55 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0 Pain Relevance 0
RT-PCRs were repeated in triplicate to confirm 2-tail t-test statistical significance of the increase in trans-SMN mRNA.
Positive_regulation (increase) of trans-SMN in tail
10) Confidence 0.55 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.07 Pain Relevance 0
SMN levels were elevated nearly three fold compared to the pM13 vector and a pMU3 vector that lacks the promoter that drives the In711 RNA (pMU3KO) (Figure 4A).
Positive_regulation (elevated) of SMN
11) Confidence 0.55 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.15 Pain Relevance 0
Similarly, the ASO-alone vector failed to induce SMN levels in vivo (data not shown).
Neg (failed) Positive_regulation (induce) of SMN
12) Confidence 0.46 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.36 Pain Relevance 0.11
Collectively, these results demonstrate that the pMU3 system results in high levels of functional SMN protein that is capable of performing UsnRNP biogenesis of the major and minor spliceosomal pathways to levels comparable to unaffected cells.
Positive_regulation (levels) of SMN
13) Confidence 0.46 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.08 Pain Relevance 0
Identification of anti-sense RNA that enhances SMN trans-splicing
Positive_regulation (enhances) of SMN
14) Confidence 0.46 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0 Pain Relevance 0
The previous experiments provided the impetus to identify a more tractable molecular mechanism to enhance SMN trans-splicing, such as antisense molecules.
Positive_regulation (enhance) of SMN
15) Confidence 0.46 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0 Pain Relevance 0
Intracerebroventricular delivery of the ASO-tsRNA vector in the SMA mouse model increases SMN protein in the central nervous system of affected animals, demonstrating a platform that can significantly elevate SMN levels in vivo and in a relevant disease context.


Positive_regulation (elevate) of SMN in central nervous system associated with central nervous system, disease, intracerebroventricular and spinal muscular atrophy
16) Confidence 0.43 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.47 Pain Relevance 0.10
The ASO-tsRNA vector significantly elevated SMN levels in primary SMA patient fibroblasts, within the central nervous system of SMA mice and increased SMN-dependent in vitro snRNP assembly.
Positive_regulation (elevated) of SMN in central nervous system associated with central nervous system and spinal muscular atrophy
17) Confidence 0.43 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2565107 Disease Relevance 0.36 Pain Relevance 0.05
Cell-based assays identified a highly efficient vector system that resulted in high levels of trans-splicing and correspondingly high SMN protein levels and increased SMN activity in SMA-derived extracts as measured by snRNP assembly assays.
Positive_regulation (increased) of SMN associated with spinal muscular atrophy
18) Confidence 0.43 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.52 Pain Relevance 0.09
We have previously described a SMN trans-splicing system that significantly elevated full-length SMN protein levels in SMA patient fibroblasts [15].
Positive_regulation (elevated) of SMN in fibroblasts associated with spinal muscular atrophy
19) Confidence 0.43 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.34 Pain Relevance 0.08
Cell-based assays identified a highly efficient vector system that resulted in high levels of trans-splicing and correspondingly high SMN protein levels and increased SMN activity in SMA-derived extracts as measured by snRNP assembly assays.
Positive_regulation (increased) of SMN associated with spinal muscular atrophy
20) Confidence 0.43 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2565107 Disease Relevance 0.52 Pain Relevance 0.09

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