Short Interspersed Nuclear Elements (SINEs)

Short interspersed nuclear elements (SINEs) are non-autonomous, non-coding transposable elements (TEs) that are about 100 to 700 base pairs in length. They are a class of retrotransposons, DNA elements that amplify themselves throughout eukaryotic genomes, often through RNA intermediates. Short interspersed nuclear elements (SINEs) are non-autonomous, non-coding transposable elements (TEs) that are about 100 to 700 base pairs in length. They are a class of retrotransposons, DNA elements that amplify themselves throughout eukaryotic genomes, often through RNA intermediates. The internal regions of SINEs originate from tRNA and remain highly conserved, suggesting positive pressure to preserve structure and function of SINEs. While SINEs are present in many species of vertebrates and invertebrates, SINEs are often lineage specific, making them useful markers of divergent evolution between species. Copy number variation and mutations in the SINE sequence make it possible to construct phylogenies based on differences in SINEs between species. SINEs are also implicated in certain types of genetic disease in humans and other eukaryotes. In essence, short interspersed nuclear elements are genetic parasites which have evolved very early in the history of eukaryotes to utilize protein machinery within the organism as well as to co-opt the machinery from similarly parasitic genomic elements. The simplicity of these elements make them incredibly successful at persisting and amplifying (through retrotransposition) within the genomes of eukaryotes. These “parasites” which have become ubiquitous in genomes can be very deleterious to organisms as discussed below. However, eukaryotes have been able to integrate short-interspersed nuclear elements into different signaling, metabolic and regulatory pathways and have become a great source of genetic variability. They seem to play a particularly important role in the regulation of gene expression and the creation of RNA genes as discussed in Sines and Gene-Regulation. This regulation extends to chromatin re-organization and the regulation of genomic architecture; furthermore, the different lineages, mutations, and activity among eukaryotes make short-interspersed nuclear elements an incredible useful tool in phylogenetic analysis. SINEs are classified as non-LTR retrotransposons because they do not contain long terminal repeats (LTRs). There are three types of SINEs common to vertebrates and invertebrates: CORE-SINEs, V-SINEs, and AmnSINEs. SINEs have 50-500 base pair internal regions which contain a tRNA-derived segment with A and B boxes that serve as an internal promoter for RNA polymerase III. SINEs are characterized by their different modules, which are essentially a sectioning of their sequence. SINEs can, but do not necessarily have to possess a head, a body, and a tail. The head, is at the 5’ end of short-interspersed nuclear elements and is an evolutionarily derived from an RNA synthesized by RNA Polymerase III such as ribosomal RNAs and tRNAs; the 5’ head is indicative of which endogenous element that SINE was derived from and was able to parasitically utilize its transcriptional machinery. For example, the 5’ of the Alu sine is derived from 7SL RNA, a sequence transcribed by RNA Polymerase III which codes for the RNA element of SRP, an abundant ribonucleoprotein. The body of SINEs possess an unknown origin but often share much homology with a corresponding LINE which thus allows SINEs to parasitically co-opt endonucleases coded by LINEs (which recognize certain sequence motifs). Lastly, the 3’ tail of SINEs is composed of short simple repeats of varying lengths; these simple repeats are sites where two (or more) short-interspersed nuclear elements can combine to form a dimeric SINE. Short-interspersed nuclear elements which do not only possess a head and tail are called simple SINEs whereas short-interspersed nuclear elements which also possess a body or are a combination of two or more SINEs are complex SINEs. Short-interspersed nuclear elements are transcribed by RNA polymerase III which is known to transcribe ribosomal RNA and tRNA, two types of RNA vital to ribosomal assembly and mRNA translation. SINEs, like tRNAs and many small-nuclear RNAs possess an internal promoter and thus are transcribed differently than most protein-coding genes. In other words, short-interspersed nuclear elements have their key promoter elements within the transcribed region itself. Though transcribed by RNA polymerase III, SINEs and other genes possessing internal promoters, recruit different transcriptional machinery and factors than genes possessing upstream promoters. Changes in chromosome structure influence gene expression primarily by affecting the accessibility of genes to transcriptional machinery. The chromosome has a very complex and hierarchical system of organizing the genome. This system of organization, which includes histones, methyl groups, acetyl groups, and a variety of proteins and RNAs allows different domains within a chromosome to be accessible to polymerases, transcription factors, and other associated proteins to different degrees. Furthermore, the shape and density of certain areas of a chromosome can affect the shape and density of neighboring (or even distant regions) on the chromosome through interaction facilitated by different proteins and elements. 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. For example, long non-coding RNAs have been known to help initiate expression of Ubx by directing the Ash1 protein to regulatory elements within the Hox gene set; Ash1 modifies chromatin structure in such a way as to increase the expression of Ubx. Short-interspersed-nuclear-elements similarly can be involved in gene regulation by modifying genomic architecture . In fact Usmanova et al. 2008 suggested that short-interspersed nuclear elements can serve as direct signals in chromatin rearrangement and structure. The paper examined the global distribution of SINEs in mouse and human chromosomes and determined that this distribution was very similar to genomic distributions of genes and CpG motifs. The distribution of SINEs to genes was significantly more similar than that of other non-coding genetic elements and even differed significantly from the distribution of long-interspersed nuclear elements. This suggested that the SINE distribution was not a mere accident caused by LINE-mediate retrotransposition but rather that SINEs possessed a role in gene-regulation. Furthermore, SINEs frequently contain motifs for YY1 polycomb proteins. YY1 is a zinc-finger protein that acts as a transcriptional repressor for a wide-variety of genes essential for development and signaling. Polycomb protein YY1 is believed to mediate the activity of histone deacetylases and histone acetyltransferases to facilitate chromatin re-organization; this is often to facilitate the formation of heterochromatin (gene-silencing state). 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. 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. For example, long non-coding RNA can directly interact with transcriptional repressors and activators, attenuating or modifying their function. This type of regulation can occur in different ways: the RNA transcript can directly bind to the transcription factor as a co-regulator; also, the RNA can regulate and modify the ability of co-regulators to associate with the transcription factor. 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. Furthermore, RNA transcripts can interfere with the functionality of the transcriptional complex by interacting or associating with RNA polymerases during the transcription or loading processes. Moreover, non-coding RNAs like SINEs can bind or interact directly with the DNA duplex coding the gene and thus prevent its transcription.