Related Experiment Video
Updated: Aug 5, 2026
11:04
RNA Next-Generation Sequencing and a Bioinformatics Pipeline to Identify Expressed LINE-1s at the Locus-Specific Level
Published on: May 19, 2019
LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis
Tinkara Korošec1, Boris Rogelj1,2, Vera Župunski1
1Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia.
International Journal of Molecular Sciences
|July 28, 2026
Summary
Increased Long Interspersed Nuclear Element-1 (LINE-1) activity may contribute to sporadic Amyotrophic Lateral Sclerosis (ALS). This retrotransposon activity can cause cellular dysfunction and neuroinflammation, offering potential therapeutic targets for ALS.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons.
- While some ALS cases are genetic, most are sporadic, suggesting complex contributing factors.
- Long interspersed nuclear element-1 (LINE-1) retrotransposons are mobile genetic elements normally suppressed in cells.
Purpose of the Study:
- To investigate the mechanistic links between LINE-1 retrotransposons and Amyotrophic Lateral Sclerosis (ALS).
- To explore LINE-1's role in the genetic architecture and progression of sporadic ALS.
- To identify potential therapeutic targets within the LINE-1-ALS pathway.
Main Methods:
- Analysis of LINE-1 retrotransposon burden in ALS genomes.
- Integration of data on LINE-1 RNA toxicity and its impact on cellular processes.
- Review of LINE-1 interactions with innate immune pathways, including the cGAS-STING axis.
Main Results:
- A higher burden of retrotransposition-competent LINE-1s (RC-L1s) was observed in ALS genomes.
- LINE-1 RNA can be toxic independently of insertions, promoting epigenetic noise and chromatin opening.
- LINE-1 intermediates can activate innate immune sensors, potentially driving neuroinflammation via the cGAS-STING pathway.
Conclusions:
- Increased RC-L1 load may contribute to the missing heritability in sporadic ALS.
- LINE-1 de-repression, driven by aging or pathology (e.g., TDP-43), leads to nuclear dysfunction and epigenetic noise.
- LINE-1 activation converges with neuroinflammation, presenting potential therapeutic targets for ALS.
Related Concept Videos
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
03:08LTR Retrotransposons
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
02:33Retroviruses
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
01:28Rabies
Rabies is a lethal zoonotic disease caused by a single-stranded, negative-sense RNA virus of the Lyssavirus genus, within the family Rhabdoviridae. Its primary mode of transmission to humans is through bites or saliva-contaminated scratches from infected mammals such as dogs, bats, raccoons, or foxes. Transmission can also occur if infectious saliva contacts abraded skin or intact mucous membranes, including the conjunctiva.Viral Entry and Early ReplicationOnce introduced at the bite or scratch...
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
02:28Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...