title: ALSINC Protein - ALS IncRNA
category: protein
---## Basic Information
RNA Name: ALSINC (ALS IncRNA)
Gene: ALSINC (C9orf72
NCBI ID: Q9H0J9
Length: ~2.5 kb transcript
Subcellular Localization: Nuclear, enriched in the nucleolus
RNA Type: Long non-coding RNA (lncRNA)
--- 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.
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
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
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
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
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
ALSINC involvement in FTD:
- FTD-ALS overlap: Shared genetic basis with C9orf72
- TDP-43 pathology: Associated with TDP-43 inclusions
- Behavioral variant FTD: Early behavioral changes linked to expression
- 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 strategies targeting ALSINC:
- ASO-mediated degradation: Reduce toxic ALSINC levels
- Splice-modulating ASOs: Alter processing of transcripts
- miRNA sponges: Compensate for lost function
Gene editing strategies:
- Promoter targeting: Modulate ALSINC expression
- Epigenetic editing: Alter chromatin state
- Allele-specific editing: Target expanded repeats specifically
- RNA-binding protein stabilizers: Prevent protein sequestration
- Transcription inhibitors: Reduce toxic transcript levels
- Nuclear export modulators: Restore transport deficits
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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.2011.09.010^1]
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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
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Mori K, et al. (2013). "The C9orf72 GGGGCC repeat forms RNA foci in neurons of the frontal cortex in patients with ALS and FTD." Acta Neuropathol. 126(1):109-112. DOI: 10.1007/s00401-013-1149-y
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Haeusler AR, et al. (2014). "C9orf72 nucleotide repeat structures initiate molecular cascades of disease." Nature. 507(7491):195-200. DOI: 10.1038/nature13124