Short interspersed nuclear element
However, eukaryotes have been able to integrate short-interspersed nuclear elements into different signaling, metabolic and regulatory pathways and SINEs have become a great source of genetic variability.
The different lineages, mutations, and activities among eukaryotes make short-interspersed nuclear elements a useful tool in phylogenetic analysis.
Non-coding RNAs such as short-interspersed nuclear elements, which have been known to associate with and contribute to chromatin structure, can thus play huge role in regulating gene expression.
In fact Usmanova et al. 2008 suggested that short-interspersed nuclear elements can serve as direct signals in chromatin rearrangement and structure.
[14] Thus, the analysis suggests that short-interspersed nuclear elements can function as a ‘signal-booster' in the polycomb-dependent silencing of gene-sets through chromatin re-organization.
[12] In essence, it is the cumulative effect of many types of interactions that leads to the difference between euchromatin, which is not tightly packed and generally more accessible to transcriptional machinery, and heterochromatin, which is tightly packed and generally not accessible to transcriptional machinery; SINEs seem to play an evolutionary role in this process.
In addition to directly affecting chromatin structure, there are a number of ways in which SINEs can potentially regulate gene expression.
[15] For example, Evf-2, a certain long non-coding RNA, has been known to function as a co-activator for certain homeobox transcription factors which are critical to nervous system development and organization.
[15] Moreover, non-coding RNAs like SINEs can bind or interact directly with the DNA duplex coding the gene and thus prevent its transcription.
Short-interspersed nuclear elements are believed to be deeply integrated into a complex regulatory network capable of fine-tuning gene expression across the eukaryotic genome.
The RNA transcribed from the short-interspersed nuclear element does not code for any protein product but is nonetheless reverse-transcribed and inserted back into an alternate region in the genome.
Open reading frame 1 (ORF 1) encodes a protein which binds to RNA and acts as a chaperone to facilitate and maintain the LINE protein-RNA complex structure.
[19] This enables the LINE mRNA to be reverse-transcribed into DNA and integrated into the genome based on the sequence-motifs recognized by the protein's endonuclease domain.
[22] These DNA breaks are utilized to prime reverse transcriptase, ultimately integrating the SINE transcript back into the genome.
[24] This result was expected and strongly supports the theory that SINEs have evolved to co-opt the RNA-binding proteins, endonucleases, and reverse-transcriptases coded by LINEs.
In taxa which do not actively transcribe and translate long-interspersed nuclear elements protein-products, SINEs do not have the theoretical foundation by which to retrotranspose within the genome.
Insertion of a SINE into the coding sequence of a gene can have deleterious effects and unregulated transposition can cause genetic disease.
The transposition and recombination of SINEs and other active nuclear elements is thought to be one of the major contributions of genetic diversity between lineages during speciation.
[20] When inserted near or within the exon, SINEs can cause improper splicing, become coding regions, or change the reading frame, often leading to disease phenotypes in humans and other animals.
[31] It was found that genes which were predicted to possess V-SINEs were targeted by microRNAs with significantly higher hybridization E-values (relative to other areas in the genome).
Many other studies must be undertaken to establish the validity and extent of short-interspersed nuclear element retrotransposons' role in regulatory gene-expression networks.
[32] This non-protein coding oligonucleotide is usually transcribed from a longer nuclear DNA sequence by RNA polymerase II which is also responsible for the transcription of most mRNAs and snRNAs in eukaryotes.
[34] This provides an alternate mechanism by which short-interspersed nuclear elements could be interacting with or mediating gene-regulatory networks involving microRNAs.
[31] This provides an evolutionarily path by which the parasitic SINEs were co-opted and utilized to form RNA-genes (such as microRNAs) which have evolved to play a role in complex gene-regulatory networks.
Multiple studies have suggested that increased SINE activity is correlated with certain gene-expression profiles and post-transcription regulation of certain genes.
In essence, short-interspersed nuclear elements have become deeply integrated in countless regulatory, metabolic and signaling pathways and thus play an inevitable role in causing disease.
The activity of SINEs however has genetic vestiges which do not seem to play a significant role, positive or negative, and manifest themselves in the genome as pseudogenes.
