Ribosomal DNA

Last updated
The gene segment of eukaryotic rDNA contains 18S, 5.8S, and 28S tracts and forms a tandem repetitive cluster; the 5S rDNA is coded separately. NTS, nontranscribed spacer, ETS, external transcribed spacer, ITS, internal transcribed spacers 1 and 2, numbered from 5' end. Eucaryot rdna.png
The gene segment of eukaryotic rDNA contains 18S, 5.8S, and 28S tracts and forms a tandem repetitive cluster; the 5S rDNA is coded separately. NTS, nontranscribed spacer, ETS, external transcribed spacer, ITS, internal transcribed spacers 1 and 2, numbered from 5' end.
Nucleolus with pre-rRNA components called Introns and Exons. Nucleolus (including pre-rRNA components).png
Nucleolus with pre-rRNA components called Introns and Exons.

Ribosomal DNA (rDNA) is a DNA sequence that codes for ribosomal RNA. These sequences regulate transcription initiation and amplification, and contain both transcribed and non-transcribed spacer segments.

Contents

In the human genome there are 5 chromosomes with nucleolus organizer regions: the acrocentric chromosomes 13 (RNR1), 14 (RNR2), 15 (RNR3), 21 (RNR4) and 22 (RNR5). The genes that are responsible for encoding the various sub-units of rRNA are located across multiple chromosomes in humans. But the genes that encode for rRNA are highly conserved across the domains, with only the copy numbers involved for the genes having varying numbers per species. [1] In Bacteria, Archaea, and chloroplasts the rRNA is composed of different (smaller) units, the large (23S) ribosomal RNA, 16S ribosomal RNA and 5S rRNA. The 16S rRNA is widely used for phylogenetic studies. [2]

Eukaryotes

The rRNA transcribed from the approximately 600 rDNA repeats forms the most abundant section of RNA found in cells of eukaryotes. [1] Ribosomes are assemblies of proteins and rRNA molecules that translate mRNA molecules to produce proteins. As shown in the figure, rDNA of eukaryotes consists of a tandem repeat of a unit segment, composed of NTS, ETS, 18S, ITS1, 5.8S, ITS2, and 28S tracts. rDNA has another gene, coding for 5S rRNA, located in the genome in most eukaryotes. [3] 5S rDNA is also present in independent tandem repeats as in Drosophila . [3] DNA regions that are repetitive often undergo recombination events. The rDNA repeats have many regulatory mechanisms that keep the DNA from undergoing mutations, thus keeping the rDNA conserved. [1]

In the nucleus, the rDNA region of the chromosome is visualized as a nucleolus which forms expanded chromosomal loops with rDNA. The rRNA transcriptional units are clustered in tandem repeats. These rDNA regions are also called nucleolus organizer regions, as they give rise to the nucleolus. In rDNA, the tandem repeats are mostly found in the nucleolus; but heterochromatic rDNA is found outside of the nucleolus. However, transcriptionally active rDNA resides inside of the nucleolus itself. [1]

Sequence homogeneity

In the large rDNA array, polymorphisms between rDNA repeat units are very low, indicating that rDNA tandem arrays are evolving through concerted evolution. [3] However, the mechanism of concerted evolution is imperfect, such that polymorphisms between repeats within an individual can occur at significant levels and may confound phylogenetic analyses for closely related organisms. [4] [5]

5S tandem repeat sequences in several Drosophila were compared with each other; the result revealed that insertions and deletions occurred frequently between species and often flanked by conserved sequences. [6] They could occur by slippage of the newly synthesized strand during DNA replication or by gene conversion. [6]

Sequence divergence

The rDNA transcription tracts have low rate of polymorphism among species, which allows interspecific comparison to elucidate phylogenetic relationship using only a few specimens. Coding regions of rDNA are highly conserved among species but ITS regions are variable due to insertions, deletions, and point mutations. Between remote species as human and frog comparison of sequences at ITS tracts is not appropriate. [7] Conserved sequences at coding regions of rDNA allow comparisons of remote species, even between yeast and human. Human 5.8S rRNA has 75% identity with yeast 5.8S rRNA. [8] In cases for sibling species, comparison of the rDNA segment including ITS tracts among species and phylogenetic analysis are made satisfactorily. [9] [10] The different coding regions of the rDNA repeats usually show distinct evolutionary rates. As a result, this DNA can provide phylogenetic information of species belonging to wide systematic levels. [11]

Recombination-stimulating activity

A fragment of yeast rDNA containing the 5S gene, non-transcribed spacer DNA, and part of the 35S gene has localized cis-acting mitotic recombination stimulating activity. [12] This DNA fragment contains a mitotic recombination hotspot, referred to as HOT1. HOT1 expresses recombination-stimulating activity when it is inserted into novel locations in the yeast genome. HOT1 includes an RNA polymerase I (PolI) transcription promoter that catalyzes 35S ribosomal rRNA gene transcription. In a PolI defective mutant, the HOT1 hotspot recombination-stimulating activity is abolished. The level of PolI transcription in HOT1 appears to determine the level of recombination. [13]

Clinical significance

Diseases can be associated with DNA mutations where DNA can be expanded, such as Huntington's disease, or lost due to deletion mutations. The same is true for mutations that occur in rDNA repeats; it has been found that if the genes that are associated with the synthesis of ribosomes are disrupted or mutated, it can result in various diseases associated with the skeleton or bone marrow. Also, any damage or disruption to the enzymes that protect the tandem repeats of the rDNA, can result in lower synthesis of ribosomes, which also lead to other defects in the cell. Neurological diseases can also arise from mutations in the rDNA tandem repeats, such as Bloom syndrome, which occurs when the number of tandem repeats increases close to a hundred-fold; compared with that of the normal number of tandem repeats. Various types of cancers can also be born from mutations of the tandem repeats in the ribosomal DNA. Cell lines can become malignant from either a rearrangement of the tandem repeats, or an expansion of the repeats in the rDNA. [14]

Related Research Articles

<span class="mw-page-title-main">Nucleolus</span> Largest structure in the nucleus of eukaryotic cells

The nucleolus is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of signal recognition particles and plays a role in the cell's response to stress. Nucleoli are made of proteins, DNA and RNA, and form around specific chromosomal regions called nucleolar organizing regions. Malfunction of nucleoli can be the cause of several human conditions called "nucleolopathies" and the nucleolus is being investigated as a target for cancer chemotherapy.

Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules. Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional, such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses. Regions that are completely nonfunctional are called junk DNA.

An inverted repeat is a single stranded sequence of nucleotides followed downstream by its reverse complement. The intervening sequence of nucleotides between the initial sequence and the reverse complement can be any length including zero. For example, 5'---TTACGnnnnnnCGTAA---3' is an inverted repeat sequence. When the intervening length is zero, the composite sequence is a palindromic sequence.

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, the evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

<span class="mw-page-title-main">Constitutive heterochromatin</span>

Constitutive heterochromatin domains are regions of DNA found throughout the chromosomes of eukaryotes. The majority of constitutive heterochromatin is found at the pericentromeric regions of chromosomes, but is also found at the telomeres and throughout the chromosomes. In humans there is significantly more constitutive heterochromatin found on chromosomes 1, 9, 16, 19 and Y. Constitutive heterochromatin is composed mainly of high copy number tandem repeats known as satellite repeats, minisatellite and microsatellite repeats, and transposon repeats. In humans these regions account for about 200Mb or 6.5% of the total human genome, but their repeat composition makes them difficult to sequence, so only small regions have been sequenced.

Internal transcribed spacer (ITS) is the spacer DNA situated between the small-subunit ribosomal RNA (rRNA) and large-subunit rRNA genes in the chromosome or the corresponding transcribed region in the polycistronic rRNA precursor transcript.

<span class="mw-page-title-main">Ribosomal RNA</span> RNA component of the ribosome, essential for protein synthesis in all living organisms

Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins by mass.

RNA polymerase 1 is, in higher eukaryotes, the polymerase that only transcribes ribosomal RNA, a type of RNA that accounts for over 50% of the total RNA synthesized in a cell.

Eukaryotic chromosome fine structure refers to the structure of sequences for eukaryotic chromosomes. Some fine sequences are included in more than one class, so the classification listed is not intended to be completely separate.

<span class="mw-page-title-main">Ribosome biogenesis</span> Cellular process

Ribosome biogenesis is the process of making ribosomes. In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons. In eukaryotes, it takes place both in the cytoplasm and in the nucleolus. It involves the coordinated function of over 200 proteins in the synthesis and processing of the three prokaryotic or four eukaryotic rRNAs, as well as assembly of those rRNAs with the ribosomal proteins. Most of the ribosomal proteins fall into various energy-consuming enzyme families including ATP-dependent RNA helicases, AAA-ATPases, GTPases, and kinases. About 60% of a cell's energy is spent on ribosome production and maintenance.

<span class="mw-page-title-main">Gene cluster</span>

A gene family is a set of homologous genes within one organism. A gene cluster is a group of two or more genes found within an organism's DNA that encode similar polypeptides, or proteins, which collectively share a generalized function and are often located within a few thousand base pairs of each other. The size of gene clusters can vary significantly, from a few genes to several hundred genes. Portions of the DNA sequence of each gene within a gene cluster are found to be identical; however, the resulting protein of each gene is distinctive from the resulting protein of another gene within the cluster. Genes found in a gene cluster may be observed near one another on the same chromosome or on different, but homologous chromosomes. An example of a gene cluster is the Hox gene, which is made up of eight genes and is part of the Homeobox gene family.

<span class="mw-page-title-main">5S ribosomal RNA</span> RNA component of the large subunit of the ribosome

The 5S ribosomal RNA is an approximately 120 nucleotide-long ribosomal RNA molecule with a mass of 40 kDa. It is a structural and functional component of the large subunit of the ribosome in all domains of life, with the exception of mitochondrial ribosomes of fungi and animals. The designation 5S refers to the molecule's sedimentation velocity in an ultracentrifuge, which is measured in Svedberg units (S).

RNA, ribosomal 4, also known as RNR4, is a human gene.

RNA, ribosomal 1, also known as RNR1, is a human gene.

RNA, ribosomal 3, also known as RNR3, is a human gene. It is a minor isoform of large subunit of ribonucleotide-diphosphate reductase; the RNR complex catalyzes rate-limiting step in dNTP synthesis, regulated by DNA replication and DNA damage checkpoint pathways via localization of small subunits; RNR3 has a paralog, RNR1, that arose from the whole genome duplication.

RNA, ribosomal 5, also known as RNR5, is a human gene. Genes for ribosomal RNA are clustered on the short arms of chromosomes 13, 14, 15, 20, 21. The gene for RNR5 exists in multiple copies on chromosome 22. Each gene cluster contains 30–40 copies and encodes a 45S RNA product that is then cleaved to form 18S, 5.8S and 28S rRNA subunits. In general, genes for RNA remain poorly annotated in most large public databases.

<span class="mw-page-title-main">5′ flanking region</span>

The 5′ flanking region is a region of DNA that is adjacent to the 5′ end of the gene. The 5′ flanking region contains the promoter, and may contain enhancers or other protein binding sites. It is the region of DNA that is not transcribed into RNA. Not to be confused with the 5′ untranslated region, this region is not transcribed into RNA or translated into a functional protein. These regions primarily function in the regulation of gene transcription. 5′ flanking regions are categorized between prokaryotes and eukaryotes.

Ribosomopathies are diseases caused by abnormalities in the structure or function of ribosomal component proteins or rRNA genes, or other genes whose products are involved in ribosome biogenesis.

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including genetics, biochemistry, and microbiology. It is split across two articles:

References

  1. 1 2 3 4 Warmerdam, Daniël O.; Wolthuis, Rob M. F. (2019-03-01). "Keeping ribosomal DNA intact: a repeating challenge". Chromosome Research. 27 (1): 57–72. doi:10.1007/s10577-018-9594-z. ISSN   1573-6849. PMC   6394564 . PMID   30556094.
  2. ↑ Weisburg WG, Barns SM, Pelletier DA, Lane DJ (January 1991). "16S ribosomal DNA amplification for phylogenetic study". Journal of Bacteriology. 173 (2): 697–703. doi:10.1128/jb.173.2.697-703.1991. PMC   207061 . PMID   1987160.
  3. 1 2 3 Richard GF, Kerrest A, Dujon B (December 2008). "Comparative genomics and molecular dynamics of DNA repeats in eukaryotes". Microbiology and Molecular Biology Reviews. 72 (4): 686–727. doi:10.1128/MMBR.00011-08. PMC   2593564 . PMID   19052325.
  4. ↑ Alvarez I, Wendel JF (December 2003). "Ribosomal ITS sequences and plant phylogenetic inference". Molecular Phylogenetics and Evolution. 29 (3): 417–34. doi:10.1016/S1055-7903(03)00208-2. PMID   14615184.
  5. ↑ Weitemier K, Straub SC, Fishbein M, Liston A (2015). "Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae)". PeerJ. 3: e718. doi: 10.7717/peerj.718 . PMC   4304868 . PMID   25653903.
  6. 1 2 Päques F, Samson ML, Jordan P, Wegnez M (November 1995). "Structural evolution of the Drosophila 5S ribosomal genes". Journal of Molecular Evolution. 41 (5): 615–21. Bibcode:1995JMolE..41..615P. doi:10.1007/bf00175820. PMID   7490776. S2CID   6911205.
  7. ↑ Sumida M, Kato Y, Kurabayashi A (April 2004). "Sequencing and analysis of the internal transcribed spacers (ITSs) and coding regions in the EcoR I fragment of the ribosomal DNA of the Japanese pond frog Rana nigromaculata". Genes & Genetic Systems. 79 (2): 105–18. doi: 10.1266/ggs.79.105 . PMID   15215676.
  8. ↑ Nazar RN, Sitz TO, Busch H (February 1976). "Sequence homologies in mammalian 5.8S ribosomal RNA". Biochemistry. 15 (3): 505–8. doi:10.1021/bi00648a008. PMID   1252408.
  9. ↑ Fengyi MY, Jiannong X, Zheming Z (1998). "Sequence differences of rDNA-ITS2 and species-diagnostic PCR assay of Anopheles sinensis and Anopheles anthropophagus from China" (PDF). J Med Coll PLA. 13: 123–128.
  10. ↑ Li, C; Lee, JS; Groebner, JL; Kim, HC; Klein, TA; O'Guinn, ML; Wilkerson, RC (2005). "A newly recognized species in the Anopheles hyrcanus group and molecular identification of related species from the Republic of South Korea (Diptera: Culicidae)" (PDF). Zootaxa. 939: 1–8. doi: 10.11646/zootaxa.939.1.1 . Archived from the original on October 1, 2012.
  11. ↑ Hillis DM, Dixon MT (December 1991). "Ribosomal DNA: molecular evolution and phylogenetic inference". The Quarterly Review of Biology. 66 (4): 411–53. doi:10.1086/417338. PMID   1784710. S2CID   32027097.
  12. ↑ Keil RL, Roeder GS (December 1984). "Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae". Cell. 39 (2 Pt 1): 377–86. doi: 10.1016/0092-8674(84)90016-3 . PMID   6094015.
  13. ↑ Serizawa N, Horiuchi T, Kobayashi T (April 2004). "Transcription-mediated hyper-recombination in HOT1". Genes to Cells. 9 (4): 305–15. doi:10.1111/j.1356-9597.2004.00729.x. PMID   15066122. S2CID   23978914.
  14. ↑ Warmerdam DO, Wolthuis RM (March 2019). "Keeping ribosomal DNA intact: a repeating challenge". Chromosome Research. 27 (1–2): 57–72. doi:10.1007/s10577-018-9594-z. PMC   6394564 . PMID   30556094.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.