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A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR.
Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.
Antisense RNA (asRNA), also referred to as antisense transcript, natural antisense transcript (NAT) or antisense oligonucleotide, is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) with which it hybridizes, and thereby blocks its translation into protein. The asRNAs have been found in both prokaryotes and eukaryotes, and can be classified into short and long non-coding RNAs (ncRNAs). The primary function of asRNA is regulating gene expression. asRNAs may also be produced synthetically and have found wide spread use as research tools for gene knockdown. They may also have therapeutic applications.
The hok/sok system is a postsegregational killing mechanism employed by the R1 plasmid in Escherichia coli. It was the first type I toxin-antitoxin pair to be identified through characterisation of a plasmid-stabilising locus. It is a type I system because the toxin is neutralised by a complementary RNA, rather than a partnered protein.
Toll-like receptor 9 is a protein that in humans is encoded by the TLR9 gene. TLR9 has also been designated as CD289. It is a member of the toll-like receptor (TLR) family. TLR9 is an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen presenting cells. TLR9 is expressed on endosomes internalized from the plasma membrane, binds DNA, and triggers signaling cascades that lead to a pro-inflammatory cytokine response. Cancer, infection, and tissue damage can all modulate TLR9 expression and activation. TLR9 is also an important factor in autoimmune diseases, and there is active research into synthetic TLR9 agonists and antagonists that help regulate autoimmune inflammation.
Natural antisense transcripts (NATs) are a group of RNAs encoded within a cell that have transcript complementarity to other RNA transcripts. They have been identified in multiple eukaryotes, including humans, mice, yeast and Arabidopsis thaliana. This class of RNAs includes both protein-coding and non-coding RNAs. Current evidence has suggested a variety of regulatory roles for NATs, such as RNA interference (RNAi), alternative splicing, genomic imprinting, and X-chromosome inactivation. NATs are broadly grouped into two categories based on whether they act in cis or in trans. Trans-NATs are transcribed from a different location than their targets and usually have complementarity to multiple transcripts with some mismatches. MicroRNAs (miRNA) are an example of trans-NATs that can target multiple transcripts with a few mismatches. Cis-natural antisense transcripts (cis-NATs) on the other hand are transcribed from the same genomic locus as their target but from the opposite DNA strand and form perfect pairs.
Long non-coding RNAs are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. Long intervening/intergenic noncoding RNAs (lincRNAs) are sequences of lncRNA which do not overlap protein-coding genes.
Skewed X-chromosome inactivation occurs when the X-inactivation of one X chromosome is favored over the other, leading to an uneven number of cells with each chromosome inactivated. It is usually defined as one allele being found on the active X chromosome in over 75% of cells, and extreme skewing is when over 90% of cells have inactivated the same X chromosome. It can be caused by primary nonrandom inactivation, either by chance due to a small cell pool or directed by genes, or by secondary nonrandom inactivation, which occurs by selection.
CDKN2B-AS, also known as ANRIL is a long non-coding RNA consisting of 19 exons, spanning 126.3kb in the genome, and its spliced product is a 3834bp RNA. It is located within the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster, in the antisense direction. Single nucleotide polymorphisms (SNPs) which alter the expression of CDKN2B-AS are associated with human healthy life expectancy, as well as with multiple diseases, including coronary artery disease, diabetes and many cancers. It binds to chromobox 7 (CBX7) within the polycomb repressive complex 1 and to SUZ12, a component of polycomb repression complex 2 and through these interactions is involved in transcriptional repression.
ZEB2-AS1 is a long non-coding RNA, which is overlapping and antisense to the ZEB2 gene. It overlaps the 5′ splice site of an intron within the 5′UTR of the ZEB2 gene. This intron contains an internal ribosome entry site (IRES), which is necessary for ZEB2 expression. ZEB2-AS1 prevents the splicing of this intron, and therefore activates ZEB2 expression.
In molecular biology, FAS antisense RNA , also known as FAS-AS1 or SAF, is a long non-coding RNA. In humans it is located on chromosome 10. In humans it is transcribed from the opposite strand of intron 1 of the FAS gene. It may regulate the expression of some isoforms of FAS. It may also play a role in the regulation of FAS-mediated apoptosis. Recently it has been shown be sehgal et al. that the alternative splicing of Fas in lymphomas is tightly regulated by a long-noncoding RNA corresponding to an antisense transcript of Fas (FAS-AS1). Levels of FAS-AS1 correlate inversely with production of sFas, and FAS-AS1 binding to the RBM5 inhibits RBM5-mediated exon 6 skipping. EZH2, often mutated or overexpressed in lymphomas, hyper-methylates the FAS-AS1 promoter and represses the FAS-AS1 expression. EZH2-mediated repression of FAS-AS1 promoter can be released by DZNeP or overcome by ectopic expression of FAS-AS1, both of which increase levels of FAS-AS1 and correspondingly decrease expression of sFas. Treatment with Bruton's tyrosine kinase inhibitor or EZH2 knockdown decreases the levels of EZH2, RBM5 and sFas, thereby enhancing Fas-mediated apoptosis. This is the first report showing functional regulation of Fas repression by its antisense RNA. Our results reveal new therapeutic targets in lymphomas and provide a rationale for the use of EZH2 inhibitors or ibrutinib in combination with chemotherapeutic agents that recruit Fas for effective cell killing.
In molecular biology, GNAS antisense RNA , also known as GNAS-AS1, is a long non-coding RNA.It is antisense to the GNAS gene. It is an imprinted gene, expressed only from the paternal allele, suggesting that it may have a role in suppression of the paternal NESP55 allele encoded by GNAS.
In molecular biology, HTT antisense RNA 1, also known as HTT-AS1, is a long non-coding RNA. It is an antisense RNA which regulates the expression of the huntingtin gene.
HOXA11-AS lncRNA is a long non-coding RNA from the antisense strand in the homeobox A. The HOX gene contains four clusters. The sense strand of the HOXA gene codes for proteins. Alternative names for HOXA11-AS lncRNA are: HOXA-AS5, HOXA11S, HOXA11-AS1, HOXA11AS, or NCRNA00076. This gene is 3,885 nucleotides long and resides at chromosome 7 (7p15.2) and is transcribed from an independent gene promoter. Being a lncRNA, it is longer than 200 nucleotides in length, in contrast to regular non-coding RNAs.
In molecular biology, NPPA antisense RNA 1, also known as NPPA-AS1 is a long non-coding RNA. It is an antisense transcript of the NPPA gene, which encodes the precursor of cardiodilatin-related peptide and atrial natriuretic factor. NPPA-AS1 is alternatively spliced. At least one isoform of NPPA-AS1 can regulate the expression of spliced and unspliced variants of NPPA, possibly by the formation of duplexes with NPPA mRNA.
In molecular biology, ZNFX1 antisense RNA 1, also known as ZNFX1-AS1 or ZFAS1, is a long non-coding RNA. It is expressed in the lung and mammary gland in mice. Its expression is down-regulated in mammary tumours, it may function as a tumour suppressor gene. The ZNFX1-AS1 gene hosts three snoRNA genes ).
MicroRNA 146a is a small non-coding RNA that in humans is encoded by the MIR146A gene.
UBE3A-ATS/Ube3a-ATS (human/mouse), otherwise known as ubiquitin ligase E3A-ATS, is the name for the antisense DNA strand that is transcribed as part of a larger transcript called LNCAT at the Ube3a locus. The Ube3a locus is imprinted and in the central nervous system expressed only from the maternal allele. Silencing of Ube3a on the paternal allele is thought to occur through the Ube3a-ATS part of LNCAT, since non-coding antisense transcripts are often found at imprinted loci. The deletion and/or mutation of Ube3a on the maternal chromosome causes Angelman Syndrome (AS) and Ube3a-ATS may prove to be an important aspect in finding a therapy for this disease. While in patients with AS the maternal Ube3a allele is inactive, the paternal allele is intact but epigenetically silenced. If unsilenced, the paternal allele could be a source of active Ube3a protein in AS patients. Therefore, understanding the mechanisms of how Ube3a-ATS might be involved in silencing the paternal Ube3a may lead to new therapies for AS. This possibility has been demonstrated by a recent study where the drug topotecan, administered to mice suffering from AS, activated expression of the paternal Ube3a gene by lowering the transcription of Ube3a-ATS.
IFNG antisense RNA 1 is a long non-coding RNA that in humans is encoded by the IFNG-AS1 gene. It is a positive regulator of interferon gamma in T and NK cells.
Epigenetics of autoimmune disorders is the role that epigenetics play in autoimmune diseases. Autoimmune disorders are a diverse class of diseases that share a common origin. These diseases originate when the immune system becomes dysregulated and mistakenly attacks healthy tissue rather than foreign invaders. These diseases are classified as either local or systemic based upon whether they affect a single body system or if they cause systemic damage.
References
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