ALSINC Protein - ALS IncRNA

ALSINC Protein - ALS IncRNA

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">ALSINC Protein - ALS IncRNA</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ALSINC</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ALSINC - ALS IncRNA</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=ALSINC" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
title: ALSINC Protein - ALS IncRNA
category: protein

Basic Information

RNA Name: ALSINC (ALS IncRNA) Gene: ALSINC ([C9orf72](/entities/c9orf72)) NCBI ID: Q9H0J9 Length: ~2.5 kb transcript Subcellular Localization: Nuclear, enriched in the nucleolus RNA Type: Long non-coding RNA (lncRNA)

Overview

--- is a protein that ### Antisense Transcriptional Regulation. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

Structure

ALSINC is a long non-coding RNA transcribed antisense to the C9orf72 gene locus:

• 5' region: Contains sequences complementary to C9orf72 promoter
• Central domain: Putative RNA-binding protein interaction sites
• 3' region: Polyadenylated tail for stability

The RNA exhibits secondary structure including:

...

ALSINC Protein - ALS IncRNA

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">ALSINC Protein - ALS IncRNA</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ALSINC</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ALSINC - ALS IncRNA</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=ALSINC" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
title: ALSINC Protein - ALS IncRNA
category: protein

Basic Information

RNA Name: ALSINC (ALS IncRNA) Gene: ALSINC ([C9orf72](/entities/c9orf72)) NCBI ID: Q9H0J9 Length: ~2.5 kb transcript Subcellular Localization: Nuclear, enriched in the nucleolus RNA Type: Long non-coding RNA (lncRNA)

Overview

--- is a protein that ### Antisense Transcriptional Regulation. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

Structure

ALSINC is a long non-coding RNA transcribed antisense to the C9orf72 gene locus:

• 5' region: Contains sequences complementary to C9orf72 promoter
• Central domain: Putative RNA-binding protein interaction sites
• 3' region: Polyadenylated tail for stability

The RNA exhibits secondary structure including:

• Stem-loop formations
• Putative miRNA binding sites
• Sponge regions for miRNAs involved in neurodegeneration

Normal Function

Antisense Transcriptional Regulation

ALSINC plays a role in regulating C9orf72 expression:

• Transcriptional interference: Competes with C9orf72 transcription
• Promoter regulation: Modifies chromatin accessibility
• Gene expression modulation: Influences downstream C9orf72 protein levels

Nuclear Organization

ALSINC contributes to nuclear architecture:

• Nuclear body localization: Associates with nuclear speckles
• Chromatin interaction: Binds to regions near C9orf72 locus
• Scaffold function: May organize nuclear proteins

RNA Processing

The lncRNA participates in RNA metabolism:

• Alternative splicing: May influence splicing of nearby genes
• mRNA stability: Affects stability of C9orf72 transcripts
• Transport: May facilitate RNA nuclear export

Role in Neurodegeneration

Amyotrophic Lateral Sclerosis

ALSINC is directly linked to ALS pathogenesis:

• C9orf72 expansion: The hexanucleotide repeat expansion in C9orf72 affects ALSINC expression
• Toxic RNA foci: Both sense and antisense transcripts form RNA foci that sequester proteins
• Dipeptide repeat proteins: Translation of expanded repeats produces toxic peptides[@renton2011]

Frontotemporal Dementia

ALSINC involvement in FTD:

• FTD-ALS overlap: Shared genetic basis with C9orf72
• [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology: Associated with TDP-43 inclusions
• Behavioral variant FTD: Early behavioral changes linked to expression

Mechanisms of Neurodegeneration

RNA toxicity: Sequestration of RNA-binding proteins

Translation disruption: Interference with normal translation

Nuclear export defects: Impaired nucleocytoplasmic transport

Stress granule formation: Abnormal stress response

Therapeutic Implications

Antisense Oligonucleotides

Therapeutic strategies targeting ALSINC:

• ASO-mediated degradation: Reduce toxic ALSINC levels
• Splice-modulating ASOs: Alter processing of transcripts
• miRNA sponges: Compensate for lost function

CRISPR Approaches

Gene editing strategies:

• Promoter targeting: Modulate ALSINC expression
• Epigenetic editing: Alter chromatin state
• Allele-specific editing: Target expanded repeats specifically

Small Molecule Modulators

• RNA-binding protein stabilizers: Prevent protein sequestration
• Transcription inhibitors: Reduce toxic transcript levels
• Nuclear export modulators: Restore transport deficits

Key Publications

Renton AE, et al. (2011). "A hexanucleotide repeat expansion in C9orf72 is the cause of chromosome 9p21-linked ALS-FTD." Neuron. 72(2):257-268. [DOI: 10.1016/j.neuron.2011.09.010[@renton2011](https://doi.org/10.1016/j.neuron.2011.09.010[^1)]

DeJesus-Hernandez M, et al. (2011). "Expanded GGGGCC hexanucleotide repeat in noncoding region of C9orf72 causes chromosome 9p-linked FTD and ALS." Neuron. 72(2):245-256. [DOI: 10.1016/j.neuron.2011.09.011](https://doi.org/10.1016/j.neuron.2011.09.011)

Mori K, et al. (2013). "The C9orf72 GGGGCC repeat forms RNA foci in [neurons](/entities/neurons) of the frontal [cortex](/brain-regions/cortex) in patients with ALS and FTD." Acta Neuropathol. 126(1):109-112. [DOI: 10.1007/s00401-013-1149-y](https://doi.org/10.1007/s00401-013-1149-y)

Haeusler AR, et al. (2014). "C9orf72 nucleotide repeat structures initiate molecular cascades of disease." Nature. 507(7491):195-200. [DOI: 10.1038/nature13124](https://doi.org/10.1038/nature13124)

See Also

• [Genes/C9orf72](/genes/c9orf72) - C9orf72 gene page
• [Mechanisms/RNA Toxicity](/mechanisms/rna-toxicity) - RNA toxicity in ALS
• [Diseases/ALS](/diseases/amyotrophic-lateral-sclerosis) - Amyotrophic lateral sclerosis
• [Diseases/FTD](/diseases/frontotemporal-dementia) - Frontotemporal dementia
• [Mechanisms/Dipeptide Repeat Proteins](/mechanisms/dipeptide-repeat-proteins) - DPR pathology

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References

[Renton AE, et al, (2011) (2011)](https://doi.org/10.1016/j.neuron.2011.09.010)

[DeJesus-Hernandez M, et al, (2011) (2011)](https://doi.org/10.1016/j.neuron.2011.09.011)

[Mori K, et al, (2013) (2013)](https://doi.org/10.1007/s00401-013-1149-y)

[Haeusler AR, et al, (2014) (2014)](https://doi.org/10.1038/nature13124)