Drosophila roX RNA

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Drosophila roX1 ncRNA

Rox1 SS.png

Conserved secondary structure of roX1 RNA
Identifiers
Symbol roX1
Rfam RF01667
Other data
RNA typeCis-regulatory element
Domain(s) Drosophila

RoX RNA is a non-coding RNA (ncRNA) present in the male-specific lethal (MSL) complex and is required for sex dosage compensation in Drosophila . As males only contain one X chromosome, male flies dosage compensate for the X chromosome by hyper-transcribing the X chromosome. This is achieved by the MSL complex binding to the X chromosome and inducing histone H4 lysine 16 acetylation and allows for the formation of euchromatin. [1] [2] These ncRNAs were first discovered in RNA extracted from neuronal cells. [3] [4]

Non-coding RNA class of RNA

A non-coding RNA (ncRNA) is an 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.

Dosage compensation Compensating for the variation in the unpaired sex chromosome:autosome chromosome ratios between sexes by activation or inactivation of genes on one or both of the sex chromosomes.

Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. Across species, different sexes are often characterized by different types and numbers of sex chromosomes. In order to neutralize the large difference in gene dosage produced by differing numbers of sex chromosomes among the sexes, various evolutionary branches have acquired various methods to equalize gene expression among the sexes. Because sex chromosomes contain different numbers of genes, different species of organisms have developed different mechanisms to cope with this inequality. Replicating the actual gene is impossible; thus organisms instead equalize the expression from each gene. For example, in humans, females (XX) silence the transcription of one X chromosome of each pair, and transcribe all information from the other, expressed X chromosome. Thus, human females have the same number of expressed X-linked genes as do human males (XY), both sexes having essentially one X chromosome per cell, from which to transcribe and express genes.

<i>Drosophila</i> genus of insects

Drosophila is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit. They should not be confused with the Tephritidae, a related family, which are also called fruit flies ; tephritids feed primarily on unripe or ripe fruit, with many species being regarded as destructive agricultural pests, especially the Mediterranean fruit fly. One species of Drosophila in particular, D. melanogaster, has been heavily used in research in genetics and is a common model organism in developmental biology. The terms "fruit fly" and "Drosophila" are often used synonymously with D. melanogaster in modern biological literature. The entire genus, however, contains more than 1,500 species and is very diverse in appearance, behavior, and breeding habitat.

Contents

Two roX RNAs have been identified in the MSL complex from Drosophila melanogaster and have been shown to be conserved across different drosophila species. The two roX RNAs, known as roX1 and roX2 have been shown to differ in primary sequence and sequence length but despite these differences they both contain a MSL binding site and are functionally redundant. [5] [6] Cloning roX genes and subsequent sequence alignment from a number of different drosophila species identified several conserved regions and it was also noticed that roX RNA is only present in male flies. [7]

<i>Drosophila melanogaster</i> Species of fruit fly

Drosophila melanogaster is a species of fly in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting with Charles W. Woodworth's proposal of the use of this species as a model organism, D. melanogaster continues to be widely used for biological research in genetics, physiology, microbial pathogenesis, and life history evolution. As of 2017, eight Nobel prizes had been awarded for research using Drosophila.

Cloning process of producing similar populations of genetically identical individuals

Cloning is the process of producing genetically identical individuals of an organism either naturally or artificially. In nature, many organisms produce clones through asexual reproduction. Cloning in biotechnology refers to the process of creating clones of organisms or copies of cells or DNA fragments. Beyond biology, the term refers to the production of multiple copies of digital media or software.

Sequence alignment

In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Aligned sequences of nucleotide or amino acid residues are typically represented as rows within a matrix. Gaps are inserted between the residues so that identical or similar characters are aligned in successive columns. Sequence alignments are also used for non-biological sequences, such as calculating the edit distance cost between strings in a natural language or in financial data.

Secondary structure predictions predicted a stem loop to be present at the 3' end of the roX RNA transcripts. Mutagenesis within this region that either altered the sequence or prevented stem loop formation was shown to be lethal in male flies as they were unable to dosage compensate as these mutations prevented MSL binding to the X chromosome. It was also shown that in the presence of mutant roX RNA the MSL complex was unable to localize on the X chromosome and mislocalize to the heterochromatic chromocenter. This suggests that roX RNA plays a role in directing MSL complex to the X chromosome. [7] Sequence alignment of roX2 identified several regions of sequence conservation known as Gub regions and are absent in roX1. Many of these Gub regions are thought to be redundant as mutating has no effect however, Gub1 which is present within the 3' stem loop region is thought to be a key motif required for roX2 as Gub1 mutations were shown to be lethal. These studies show that roX RNA are essential for dosage compensation where that the 3' stem loop region in the roX RNA are crucial for MSL localization and it is thought to be the motif that allows the two roX RNAs to be functionally redundant.

Mutagenesis is a process by which the genetic information of an organism is changed, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures. In nature mutagenesis can lead to cancer and various heritable diseases, but it is also a driving force of evolution. Mutagenesis as a science was developed based on work done by Hermann Muller, Charlotte Auerbach and J. M. Robson in the first half of the 20th century.

Mutant organism or a new genetic character arising or resulting from an instance of mutation, which is an alteration of the DNA sequence of a gene or chromosome of an organism

In biology and especially genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. The term mutant is also applied to a virus with an alteration in its nucleotide sequence whose genome is RNA, rather than DNA. In multicellular eukaryotes, a DNA sequence may be altered in an individual somatic cell that then gives rise to a mutant somatic cell lineage as happens in cancer progression. Also in eukaryotes, alteration of a mitochondrial or plastid DNA sequence may give rise to a mutant lineage that is inherited separately from mutant genotypes in the nuclear genome. The natural occurrence of genetic mutations is integral to the process of evolution. The study of mutants is an integral part of biology; by understanding the effect that a mutation in a gene has, it is possible to establish the normal function of that gene.

See also

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Heterochromatin A compact and highly condensed form of chromatin.

Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed, however according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.

Spliceosome Molecular machine that removes intron RNA from the primary transcript

A spliceosome is a large and complex molecular machine found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and approximately 80 proteins. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. An analogy is a film editor, who selectively cuts out irrelevant or incorrect material from the initial film and sends the cleaned-up version to the director for the final cut.

Condensin

Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis.

The 5′ untranslated region is the region of an mRNA that is directly upstream from the initiation codon. This region is important for the regulation of translation of a transcript by differing mechanisms in viruses, prokaryotes and eukaryotes. While called untranslated, the 5′ UTR or a portion of it is sometimes translated into a protein product. This product can then regulate the translation of the main coding sequence of the mRNA. In many organisms, however, the 5′ UTR is completely untranslated, instead forming complex secondary structure to regulate translation. The 5′ UTR has been found to interact with proteins relating to metabolism; and proteins translate sequences within the 5′ UTR. In addition, this region has been involved in transcription regulation, such as the sex-lethal gene in Drosophila. Regulatory elements within 5′ UTRs have also been linked to mRNA export.

Trinucleotide repeat disorders are a set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where trinucleotide repeats in certain genes or introns exceed the normal, stable threshold, which differs per gene. The mutation is a subset of unstable microsatellite repeats that occur throughout all genomic sequences. If the repeat is present in a healthy gene, a dynamic mutation may increase the repeat count and result in a defective gene. If the repeat is present in an intron it can cause toxic effects by forming spherical clusters called RNA foci in cell nuclei.

Meiotic drive is a type of intragenomic conflict, whereby one or more loci within a genome will affect a manipulation of the meiotic process in such a way as to favor the transmission of one or more alleles over another, regardless of its phenotypic expression. More simply, meiotic drive is when one copy of a gene is passed on to offspring more than the expected 50% of the time. According to Buckler et al., "Meiotic drive is the subversion of meiosis so that particular genes are preferentially transmitted to the progeny. Meiotic drive generally causes the preferential segregation of small regions of the genome".

X hyperactivation

X hyperactivation refers to the process in Drosophila by which genes on the X chromosome in male flies become twice as active as genes on the X chromosome in female flies.

ZW sex-determination system chromosomal system that determines the sex of offspring in birds, some fish and crustaceans such as the giant river prawn, some insects (including butterflies and moths), and some reptiles, including Komodo dragons

The ZW sex-determination system is a chromosomal system that determines the sex of offspring in birds, some fish and crustaceans such as the giant river prawn, some insects, and some reptiles, including Komodo dragons. The letters Z and W are used to distinguish this system from the XY sex-determination system.

PrrB/RsmZ RNA family

The PrrB/RsmZ RNA family are a group of related non-coding RNA molecules found in bacteria. PrrB RNA is able to phenotypically complement gacS and gacA mutants and is itself regulated by the GacS-GacA two-component signal transduction system. Inactivation of the prrB gene in Pseudomonas fluorescens F113 resulted in a significant reduction of 2, 4-diacetylphloroglucinol (Phl) and hydrogen cyanide (HCN) production, while increased metabolite production was observed when prrB was overexpressed. The prrB gene sequence contains a number of imperfect repeats of the consensus sequence 5'-AGGA-3', and sequence analysis predicted a complex secondary structure featuring multiple putative stem-loops with the consensus sequences predominantly positioned at the single-stranded regions at the ends of the stem-loops. This structure is similar to the CsrB and RsmB regulatory RNAs, suggesting this RNA also interacts with a CsrA-like protein.

The gene extramachrochaetae (emc) is a Drosophila melanogaster gene that codes for the Emc protein, which has a wide variety of developmental roles. It was named, as is common for Drosophila genes, after the phenotypic change caused by a mutation in the gene.

SLBP protein-coding gene in the species Homo sapiens

Histone RNA hairpin-binding protein or stem-loop binding protein (SLBP) is a protein that in humans is encoded by the SLBP gene.

XIST non-coding RNA in the species Homo sapiens

Xist is an RNA gene on the X chromosome of the placental mammals that acts as a major effector of the X inactivation process. It is a component of the Xic – X-chromosome inactivation centre – along with two other RNA genes and two protein genes. The Xist RNA, a large transcript, is expressed on the inactive chromosome and not on the active one. It is processed in a similar way to mRNAs, through splicing and polyadenylation. However, it remains untranslated. It has been suggested that this RNA gene evolved at least partly from a protein coding gene that became a pseudogene. The inactive X chromosome is coated with this transcript, which is essential for the inactivation. X chromosomes lacking Xist will not be inactivated, while duplication of the Xist gene on another chromosome causes inactivation of that chromosome. The human XIST gene was discovered by Carolyn J. Brown in the laboratory of Hunt Willard.

Long non-coding RNAs are defined as transcripts longer than 200 nucleotides that are not translated into protein. This somewhat 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.

Tsix non-coding RNA in the species Homo sapiens

Tsix is a non-coding RNA gene that is antisense to the Xist RNA. Tsix binds Xist during X chromosome inactivation. The name Tsix comes from the reverse of Xist, which stands for X-inactive specific transcript.

Gene gating is a phenomenon by which transcriptionally active genes are brought next to nuclear pore complexes (NPCs) so that nascent transcripts can quickly form mature mRNA associated with export factors. Gene gating was first hypothesised by Günter Blobel in 1985. It has been shown to occur in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster as well as mammalian model systems.

Topologically associating domain

A topologically associating domain (TAD) is a self-interacting genomic region, meaning that DNA sequences within a TAD physically interact with each other more frequently than with sequences outside the TAD. These three-dimensional chromosome structures are present in animals as well as some plants, fungi, and bacteria. TADs can range in size from thousands to millions of DNA bases.

Mitzi Kuroda is a Professor of Genetics at Harvard Medical School and Brigham and Women’s Hospital. She was an HHMI Investigator at Brigham and Women’s Hospital from 1993-2007. She has identified many genes and enzymes involved in epigenetic regulation in the fruit fly. In addition, her research has shown the importance of epigenetics in cancer. Her laboratory has identified chromatin remodeling signals and processes that predispose cells to be transformed into cancer cells.

Spiroplasma poulsonii are bacteria of the genus Spiroplasma that are commonly endosymbionts of flies. These bacteria live in the hemolymph of the flies, where they can act as reproductive manipulators or defensive symbionts.

References

  1. Meller, V.; Gordadze, P.; Park, Y.; Chu, X.; Stuckenholz, C.; Kelley, R.; Kuroda, M. (Feb 2000). "Ordered assembly of roX RNAs into MSL complexes on the dosage-compensated X chromosome in Drosophila". Current Biology. 10 (3): 136–143. doi:10.1016/S0960-9822(00)00311-0. ISSN   0960-9822. PMID   10679323.
  2. Hamada, N.; Park, J.; Gordadze, R.; Kuroda, I. (Oct 2005). "Global regulation of X chromosomal genes by the MSL complex in Drosophila melanogaster" (Free full text). Genes & Development. 19 (19): 2289–2294. doi:10.1101/gad.1343705. ISSN   0890-9369. PMC   1240037 Lock-green.svg. PMID   16204180.
  3. Meller V; Wu K; Roman G.; Kuroda M; Davis R (1997). "roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system". Cell. 88 (4): 445–457. doi:10.1016/S0092-8674(00)81885-1. PMID   9038336.
  4. Amrein H, Axel R (1997). "Genes expressed in neurons of adult male Drosophila". Cell. 88 (4): 459–69. doi:10.1016/S0092-8674(00)81886-3. PMID   9038337.
  5. Franke, A.; Baker, B. (Jul 1999). "The rox1 and rox2 RNAs are essential components of the compensasome, which mediates dosage compensation in Drosophila". Molecular Cell. 4 (1): 117–122. doi:10.1016/S1097-2765(00)80193-8. ISSN   1097-2765. PMID   10445033.
  6. Meller, H.; Rattner, P. (Mar 2002). "The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex". The EMBO Journal (Free full text). 21 (5): 1084–1091. doi:10.1093/emboj/21.5.1084. ISSN   0261-4189. PMC   125901 Lock-green.svg. PMID   11867536.
  7. 1 2 Park, W.; Kang, E.; Sypula, G.; Choi, J.; Oh, H.; Park, Y. (Nov 2007). "An Evolutionarily Conserved Domain of roX2 RNA is Sufficient for Induction of H4-Lys16 Acetylation on the Drosophila X Chromosome" (Free full text). Genetics. 177 (3): 1429–1437. doi:10.1534/genetics.107.071001. ISSN   0016-6731. PMC   2147973 Lock-green.svg. PMID   18039876.

Rfam is a database containing information about non-coding RNA (ncRNA) families and other structured RNA elements. It is an annotated, open access database originally developed at the Wellcome Trust Sanger Institute in collaboration with Janelia Farm, and currently hosted at the European Bioinformatics Institute. Rfam is designed to be similar to the Pfam database for annotating protein families.