Twintron

Last updated

In molecular biology, a twintron is an intron-within-intron excised by sequential splicing reactions. A twintron is presumably formed by the insertion of a mobile intron into an existing intron.

Contents

Discovery

Twintrons were discovered by Donald W. Copertino and Richard B. Hallick as a group II intron within another group II intron in Euglena chloroplast genome. [1] They found that splicing of both the internal and external introns occurs via lariat intermediates. Additionally, twintron splicing was found to proceed by a sequential pathway, the internal intron being removed prior to the excision of the external intron.

Since the original discovery, there have been other reports of Group III twintrons and GroupII/III twintrons in the chloroplast of Euglena gracilis . In 1993 a new type of complex twintron composed of four individual group III introns has been characterized. [2] The external intron was interrupted by an internal intron containing two additional introns. In 1995 scientists discovered the first non-Euglena twintron in cryptomonad alga Pyrenomonas salina. [3] In 2004, several twintrons were discovered in Drosophila . [4]

Distribution

The majority of these twintrons have been characterized within the Euglena chloroplast genome but these elements have also been found in cryptomonad algae (Pyrenomonas salina), [5] and group I intron based twintrons (group I inserted within a group I intron) have been described in Didymium iridis. [6] Since the discovery of the psbF twintron, several categories of twintrons have been characterized. A twintron can be simple (external intron interrupted by 1 internal intron), or complex (external intron interrupted by multiple internal introns). [7] Most probably, the internal and external introns comprising the twintron element are from the same category; group I internal to group I, [8] group II internal to group II, [9] and group III internal to group III. [10] Mixed twintrons (consisting of introns belonging to different categories) were characterized from the Euglena gracilis rps3 gene in which an internal group II intron is found to interrupt an external group III intron. [11] In Rhodomonas salina (=Pyrenomonas salina) twintrons (nested group II/group III introns) were identified where the internal intron lost its splicing capacity, essentially merging with the outer intron forming one splicing unit. [12] Recently, two novel twintrons have been uncovered within the fungal mitochondrial genome, one at position mS917 of the Cryphonectria parasitica mt-rns gene, where a group ID intron encoding a LAGLIDADG ORF invaded another ORF-less group ID intron. Another twintron complex was detected at position mS1247 of the Chaetomium thermophilumhere mt-rns gene, a group IIA1 intron invaded the open reading frame embedded within a group IC2 intron. [13] The mS1247 twintron represents the first recorded fungal mitochondrial mixed twintron consisting of group II intron as an internal intron and a group I intron as an external intron. In mS1247 twintron, splicing of the internal group IIA1 intron reconstitutes the open reading frame encoded within the group IC2 intron and thus facilitates the expression of the encoded homing endonuclease. The mS1247 twintron encod ORF have been biochemically characterized and the results showed that it is an active homing endonuclease that could potentially mobilize the twintron to rns genes that have not yet been invaded by this mobile composite element. [14]

See also

Related Research Articles

<span class="mw-page-title-main">Exon</span> A region of a transcribed gene present in the final functional mRNA molecule

An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature RNA. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome.

An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word intron is derived from the term intragenic region, i.e. a region inside a gene. The term intron refers to both the DNA sequence within a gene and the corresponding RNA sequence in RNA transcripts. The non-intron sequences that become joined by this RNA processing to form the mature RNA are called exons.

<span class="mw-page-title-main">RNA splicing</span> Process in molecular biology

RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns and splicing back together exons. For nuclear-encoded genes, splicing occurs in the nucleus either during or immediately after transcription. For those eukaryotic genes that contain introns, splicing is usually needed to create an mRNA molecule that can be translated into protein. For many eukaryotic introns, splicing occurs in a series of reactions which are catalyzed by the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs). There exist self-splicing introns, that is, ribozymes that can catalyze their own excision from their parent RNA molecule. The process of transcription, splicing and translation is called gene expression, the central dogma of molecular biology.

<span class="mw-page-title-main">Protein splicing</span> The post-translational removal of peptide sequences from within a protein sequence

Protein splicing is an intramolecular reaction of a particular protein in which an internal protein segment is removed from a precursor protein with a ligation of C-terminal and N-terminal external proteins on both sides. The splicing junction of the precursor protein is mainly a cysteine or a serine, which are amino acids containing a nucleophilic side chain. The protein splicing reactions which are known now do not require exogenous cofactors or energy sources such as adenosine triphosphate (ATP) or guanosine triphosphate (GTP). Normally, splicing is associated only with pre-mRNA splicing. This precursor protein contains three segments—an N-extein followed by the intein followed by a C-extein. After splicing has taken place, the resulting protein contains the N-extein linked to the C-extein; this splicing product is also termed an extein.

Intragenomic conflict refers to the evolutionary phenomenon where genes have phenotypic effects that promote their own transmission in detriment of the transmission of other genes that reside in the same genome. The selfish gene theory postulates that natural selection will increase the frequency of those genes whose phenotypic effects cause their transmission to new organisms, and most genes achieve this by cooperating with other genes in the same genome to build an organism capable of reproducing and/or helping kin to reproduce. The assumption of the prevalence of intragenomic cooperation underlies the organism-centered concept of inclusive fitness. However, conflict among genes in the same genome may arise both in events related to reproduction and altruism.

Marlene Belfort is an American biochemist known for her research on the factors that interrupt genes and proteins. She is a fellow of the American Academy of Arts and Sciences and has been admitted to the United States National Academy of Sciences.

Group III intron is a class of introns found in mRNA genes of chloroplasts in euglenid protists. They have a conventional group II-type dVI with a bulged adenosine, a streamlined dI, no dII-dV, and a relaxed splice site consensus. Splicing is done with two transesterification reactions with a dVI bulged adenosine as initiating nucleophile; the intron is excised as a lariat. Not much is known about how they work, although an isolated chloroplast transformation system has been constructed.

<span class="mw-page-title-main">Group II intron</span> Class of self-catalyzing ribozymes

Group II introns are a large class of self-catalytic ribozymes and mobile genetic elements found within the genes of all three domains of life. Ribozyme activity can occur under high-salt conditions in vitro. However, assistance from proteins is required for in vivo splicing. In contrast to group I introns, intron excision occurs in the absence of GTP and involves the formation of a lariat, with an A-residue branchpoint strongly resembling that found in lariats formed during splicing of nuclear pre-mRNA. It is hypothesized that pre-mRNA splicing may have evolved from group II introns, due to the similar catalytic mechanism as well as the structural similarity of the Group II Domain V substructure to the U6/U2 extended snRNA. Finally, their ability to site-specifically insert into DNA sites has been exploited as a tool for biotechnology. For example, group II introns can be modified to make site-specific genome insertions and deliver cargo DNA such as reporter genes or lox sites

<span class="mw-page-title-main">I-CreI</span>

I-CreI is a homing endonuclease whose gene was first discovered in the chloroplast genome of Chlamydomonas reinhardtii, a species of unicellular green algae. It is named for the facts that: it resides in an Intron; it was isolated from Clamydomonas reinhardtii; it was the first (I) such gene isolated from C. reinhardtii. Its gene resides in a group I intron in the 23S ribosomal RNA gene of the C. reinhardtii chloroplast, and I-CreI is only expressed when its mRNA is spliced from the primary transcript of the 23S gene. I-CreI enzyme, which functions as a homodimer, recognizes a 22-nucleotide sequence of duplex DNA and cleaves one phosphodiester bond on each strand at specific positions. I-CreI is a member of the LAGLIDADG family of homing endonucleases, all of which have a conserved LAGLIDADG amino acid motif that contributes to their associative domains and active sites. When the I-CreI-containing intron encounters a 23S allele lacking the intron, I-CreI enzyme "homes" in on the "intron-minus" allele of 23S and effects its parent intron's insertion into the intron-minus allele. Introns with this behavior are called mobile introns. Because I-CreI provides for its own propagation while conferring no benefit on its host, it is an example of selfish DNA.

<span class="mw-page-title-main">Homing endonuclease</span>

The homing endonucleases are a collection of endonucleases encoded either as freestanding genes within introns, as fusions with host proteins, or as self-splicing inteins. They catalyze the hydrolysis of genomic DNA within the cells that synthesize them, but do so at very few, or even singular, locations. Repair of the hydrolyzed DNA by the host cell frequently results in the gene encoding the homing endonuclease having been copied into the cleavage site, hence the term 'homing' to describe the movement of these genes. Homing endonucleases can thereby transmit their genes horizontally within a host population, increasing their allele frequency at greater than Mendelian rates.

<span class="mw-page-title-main">Group I catalytic intron</span>

Group I introns are large self-splicing ribozymes. They catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of nine paired regions (P1-P9). These fold to essentially two domains – the P4-P6 domain and the P3-P9 domain. The secondary structure mark-up for this family represents only this conserved core. Group I introns often have long open reading frames inserted in loop regions.

<span class="mw-page-title-main">TSEN15</span> Protein-coding gene in the species Homo sapiens

tRNA-splicing endonuclease subunit Sen15 is an enzyme that in humans is encoded by the TSEN15 gene.

The Lariat capping ribozyme is a ~180 nt ribozyme with an apparent resemblance to a group I ribozyme. It is found within a complex type of group I introns also termed twin-ribozyme introns. Rather than splicing, it catalyses a branching reaction in which the 2'OH of an internal residue is involved in a nucleophilic attack at a nearby phosphodiester bond. As a result, the RNA is cleaved at an internal processing site (IPS), leaving a 3'OH and a downstream product with a 3 nt lariat at its 5' end. The lariat has the first and the third nucleotide joined by a 2',5' phosphodiester bond and is referred to as 'the lariat cap' because it caps an intron-encoded mRNA. The resulting lariat cap seems to contribute by increasing the half-life of the HE mRNA, thus conferring an evolutionary advantage to the HE.

<span class="mw-page-title-main">Chloroplast DNA</span> DNA located in cellular organelles called chloroplasts

Chloroplast DNA (cpDNA) is the DNA located in chloroplasts, which are photosynthetic organelles located within the cells of some eukaryotic organisms. Chloroplasts, like other types of plastid, contain a genome separate from that in the cell nucleus. The existence of chloroplast DNA was identified biochemically in 1959, and confirmed by electron microscopy in 1962. The discoveries that the chloroplast contains ribosomes and performs protein synthesis revealed that the chloroplast is genetically semi-autonomous. The first complete chloroplast genome sequences were published in 1986, Nicotiana tabacum (tobacco) by Sugiura and colleagues and Marchantia polymorpha (liverwort) by Ozeki et al. Since then, a great number of chloroplast DNAs from various species have been sequenced.

Meganucleases are endodeoxyribonucleases characterized by a large recognition site ; as a result this site generally occurs only once in any given genome. For example, the 18-base pair sequence recognized by the I-SceI meganuclease would on average require a genome twenty times the size of the human genome to be found once by chance. Meganucleases are therefore considered to be the most specific naturally occurring restriction enzymes.

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

<span class="mw-page-title-main">BZIP intron RNA motif</span>

The bZIP intron RNA motif is an RNA structure guiding splicing of a non-canonical intron from bZIP-containing genes called HAC1 in yeast, XBP1 in Metazoa, Hxl1 or Cib1 in Basidiomycota and bZIP60 in plants. Splicing is performed independently of the spliceosome by Ire1, a kinase with endoribonuclease activity. Exons are joined by a tRNA ligase. Recognition of the intron splice sites is mediated by a base-paired secondary structure of the mRNA that forms at the exon/intron boundaries. Splicing of the bZIP intron is a key regulatory step in the unfolded protein response (UPR). The Ire-mediated unconventional splicing was first described for HAC1 in S. cerevisiae.

<span class="mw-page-title-main">CRM domain</span>

In molecular biology, the CRM domain is an approximately 100-amino acid RNA-binding domain. The name CRM has been suggested to reflect the functions established for four characterised members of the family: Zea mays (Maize) CRS1, CAF1 and CAF2 proteins and the Escherichia coli protein YhbY. Proteins containing the CRM domain are found in eubacteria, archaea, and plants. The CRM domain is represented as a stand-alone protein in archaea and bacteria, and in single- and multi-domain proteins in plants. It has been suggested that prokaryotic CRM proteins existed as ribosome-associated proteins prior to the divergence of archaea and bacteria, and that they were co-opted in the plant lineage as RNA binding modules by incorporation into diverse protein contexts. Plant CRM domains are predicted to reside not only in the chloroplast, but also in the mitochondrion and the nucleo/cytoplasmic compartment. The diversity of the CRM domain family in plants suggests a diverse set of RNA targets.

<span class="mw-page-title-main">Alan Lambowitz</span> American academic

Alan Lambowitz is a professor for the University of Texas at Austin in Molecular Biosciences and Oncology and has been instrumental in many bio-molecular processes and concepts, such as intron splicing and mitochondrial ribosomal assembly.

References

  1. ↑ Copertino DW, Hallick RB (February 1991). "Group II twintron: an intron within an intron in a chloroplast cytochrome b-559 gene". The EMBO Journal. 10 (2): 433–42. doi:10.1002/j.1460-2075.1991.tb07965.x. PMC   452664 . PMID   1899376.
  2. ↑ Drager RG, Hallick RB (May 1993). "A complex twintron is excised as four individual introns". Nucleic Acids Research. 21 (10): 2389–94. doi:10.1093/nar/21.10.2389. PMC   309537 . PMID   7685079.
  3. ↑ Maier UG, Rensing SA, Igloi GL, Maerz M (January 1995). "Twintrons are not unique to the Euglena chloroplast genome: structure and evolution of a plastome cpn60 gene from a cryptomonad". Molecular & General Genetics. 246 (1): 128–31. doi:10.1007/BF00290141. PMID   7823908. S2CID   10545108.
  4. ↑ Scamborova P, Wong A, Steitz JA (March 2004). "An intronic enhancer regulates splicing of the twintron of Drosophila melanogaster prospero pre-mRNA by two different spliceosomes". Molecular and Cellular Biology. 24 (5): 1855–69. doi:10.1128/MCB.24.5.1855-1869.2004. PMC   350559 . PMID   14966268.
  5. ↑ Maier, UG; Rensing, SA; Igloi, GL; Maerz, M (6 January 1995). "Twintrons are not unique to the Euglena chloroplast genome: structure and evolution of a plastome cpn60 gene from a cryptomonad". Molecular & General Genetics. 246 (1): 128–31. doi:10.1007/bf00290141. PMID   7823908. S2CID   10545108.
  6. ↑ Einvik, C; Nielsen, H; Westhof, E; Michel, F; Johansen, S (May 1998). "Group I-like ribozymes with a novel core organization perform obligate sequential hydrolytic cleavages at two processing sites". RNA. 4 (5): 530–41. doi:10.1017/s1355838298971758. PMC   1369637 . PMID   9582095.
  7. ↑ Robart, AR; Zimmerly, S (2005). "Group II intron retroelements: function and diversity". Cytogenetic and Genome Research. 110 (1–4): 589–97. doi:10.1159/000084992. PMID   16093712. S2CID   36481739.
  8. ↑ Einvik, C; Elde, M; Johansen, S (17 September 1998). "Group I twintrons: genetic elements in myxomycete and schizopyrenid amoeboflagellate ribosomal DNAs". Journal of Biotechnology. 64 (1): 63–74. doi:10.1016/s0168-1656(98)00104-7. PMID   9823659.
  9. ↑ Copertino DW, Hallick RB (February 1991). "Group II twintron: an intron within an intron in a chloroplast cytochrome b-559 gene". The EMBO Journal. 10 (2): 433–42. doi:10.1002/j.1460-2075.1991.tb07965.x. PMC   452664 . PMID   1899376.
  10. ↑ Copertino, DW; Hall, ET; Van Hook, FW; Jenkins, KP; Hallick, RB (25 March 1994). "A group III twintron encoding a maturase-like gene excises through lariat intermediates". Nucleic Acids Research. 22 (6): 1029–36. doi:10.1093/nar/22.6.1029. PMC   307926 . PMID   7512259.
  11. ↑ Copertino, DW; Hallick, RB (December 1993). "Group II and group III introns of twintrons: potential relationships with nuclear pre-mRNA introns". Trends in Biochemical Sciences. 18 (12): 467–71. doi:10.1016/0968-0004(93)90008-b. PMID   8108859.
  12. ↑ Khan, H; Archibald, JM (May 2008). "Lateral transfer of introns in the cryptophyte plastid genome". Nucleic Acids Research. 36 (9): 3043–53. doi:10.1093/nar/gkn095. PMC   2396441 . PMID   18397952.
  13. ↑ Hafez, M; Majer, A; Sethuraman, J; Rudski, SM; Michel, F; Hausner, G (April 2013). "The mtDNA rns gene landscape in the Ophiostomatales and other fungal taxa: twintrons, introns, and intron-encoded proteins". Fungal Genetics and Biology. 53: 71–83. doi:10.1016/j.fgb.2013.01.005. PMID   23403360.
  14. ↑ Guha, TK; Hausner, G (April 2014). "A homing endonuclease with a switch: characterization of a twintron encoded homing endonuclease". Fungal Genetics and Biology. 65: 57–68. doi:10.1016/j.fgb.2014.01.004. PMID   24508098.
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.