Chimeric RNA

Last updated

Chimeric RNA, sometimes referred to as a fusion transcript, is composed of exons from two or more different genes that have the potential to encode novel proteins. [1] These mRNAs are different from those produced by conventional splicing as they are produced by two or more gene loci.

Contents

Review of RNA Production

The pathway from DNA to protein expression fundamental to the central dogma of biology. Central Dogma of Molecular Biochemistry with Enzymes.jpg
The pathway from DNA to protein expression fundamental to the central dogma of biology.

In 1956, Francis Crick proposed what is now known as the "central dogma" of biology: [3]

DNA encodes the genetic information required for an organism to carry out its life cycle. In effect, DNA serves as the "hard drive" which stores genetic data. DNA is replicated and serves as its own template for replication. DNA forms a double helix structure and is a composed of a sugar-phosphate backbone and nitrogenous bases; this can be thought of as a ladder structure where the sides of the ladder are constructed of deoxyribose sugar and phosphate while the rungs of the ladder are composed of paired nitrogenous bases. [4] There are four bases in a DNA molecule: adenine (A), cytosine (C), thymine (T), and guanine (G). Nucleotides are a structural component of DNA and RNA, being made of a molecule of sugar and a molecule of phosphoric acid. The double helix structure of DNA is composed of two antiparallel strands which are oriented in opposite directions. DNA is composed of base pairs in which adenine pairs with thymine and guanine pairs with cytosine. While DNA serves as template for production of ribonucleic acid (RNA), RNA is usually responsible for making protein. The process of making RNA from DNA is called transcription. RNA uses a similar set of bases except that thymine is replaced with uracil. A group of enzymes called RNA polymerases (isolated by biochemists Jerard Hurwitz and Samuel B. Weiss) function in the presence of DNA. These enzymes produce RNA using segments of chromosomal DNA as a template. Unlike replication, where a complete copy of DNA is made, transcription copies only the gene that is to be expressed as a protein. [5]

Initially, it was thought that RNA served as a structural template for protein synthesis, essentially ordering amino acids by a series of cavities shaped specifically so that only specific amino acids would fit. Crick was not satisfied with this hypothesis given that the four bases of RNA are hydrophilic and that many amino acids prefer interactions with hydrophobic groups. Additionally, some amino acids are very structurally similar and Crick felt that accurate discrimination would not be possible given the similarities. Crick then proposed that prior to incorporation into proteins, amino acids are first attached to adapter molecules which have unique surface features that can bind to specific bases on the RNA templates. [5] These adapter molecules are called transfer RNA (tRNA).

Through a series of experiments involving E. coli and the T4 phage in 1960, [5] it was shown that messenger RNA (mRNA) carriers information from DNA to the ribosomal sites of protein synthesis. The tRNA-amino acid precursors are brought into position by ribosomes where they can read the information provided mRNA templates to synthesize protein.

RNA Splicing

Creating a protein consists of two main steps: transcription of DNA into RNA and translation of RNA into protein. After DNA is transcribed into RNA, the molecule is known as pre-messenger RNA (mRNA) and it consists of exons and introns that can be split apart and rearranged in many different ways. Historically, exons are considered the coding sequence and introns are considered the “junk” DNA. Although this has been shown to be false, it is true that exons are often merged. Depending on the needs of the cell, regulatory mechanisms choose which exons, and sometimes introns, to join. This process of removing pieces of a pre- mRNA transcript and combining them with other pieces is called splicing. The human genome encodes approximately 25,000 genes but there are significantly more proteins produced. This is accomplished through RNA splicing. The exons of these 25,000 genes can be spliced in many different ways to create countless combinations of RNA transcripts and ultimately countless proteins. Normally, exons from the same pre-mRNA transcript are spliced together. However, occasionally gene products or pre-mRNA transcripts are spliced together so that exons from different transcripts are mixed together in a fusion product known as chimeric RNA. Chimeric RNA often incorporates exons from highly expressed genes, [1] but the chimeric transcript itself is usually expressed at low levels.

This chimeric RNA can then be translated into a fusion protein. Fusion proteins are very tissue-specific [1] and they are frequently associated with cancers such as colorectal, prostate, [6] and mesotheliomas. [7] They significantly exploit signal peptides and transmembrane proteins which can alter the localization of proteins, possibly contributing to the disease phenotype.

Discovery of Chimeric RNA

One of the first studies to investigate the generation of chimeric RNA examined the fusion of the first three exons of a gene known as JAZF1 to the last 15 exons of a gene known as JJAZ1. [8] This exact transcript, and the resulting protein, was found specifically in endometrial tissue. While often found in endometrial cancers, these transcripts are expressed in normal tissue as well. Originally thought to be the result of chromosomal fusions, one group investigated whether this was accurate. Using Southern blotting and fluorescence in situ hybridization (FISH) on the genome, the researchers found no evidence of DNA rearrangement. They decided to investigate further by combining human endometrial cells with rhesus fibroblasts and found chimeric products containing sequences from both species. These data suggested that chimeric RNA is generated by splicing parts of genes together rather than chromosomal re-arrangements. They also performed mass spectrometry on the translated protein to verify that the chimeric RNA is translated into protein.

Recently, advances in next-generation sequencing have decreased the cost of sequencing significantly, allowing more RNAseq projects to be conducted. These RNAseq projects are able to detect novel RNA transcripts instead of the traditional microarray in which only known transcripts can be detected. Deep sequencing enables detection of transcripts even at very low levels. This has allowed researchers to detect many more chimeric RNAs and fusion proteins and has facilitated understanding their role in health and disease.

Chimeric protein products

Numerous putative chimeric transcripts have been identified among the expressed sequence tags using high throughput RNA sequencing technology. In humans, chimeric transcripts can be generated in several ways such as trans-splicing of pre-mRNAs, RNA transcription runoff, from other errors in RNA transcription or they can also be the result of gene fusion following inter-chromosomal translocations or rearrangements. Among the few corresponding protein products that have been characterized so far, most result from chromosomal translocations and are associated with cancer. For instance, gene fusion in chronic myelogenous leukemia (CML) leads to an mRNA transcript that encompasses the 5′ end of the breakpoint cluster region protein (BCR) gene and the 3′ end of the Abelson murine leukemia viral oncogene homolog 1 (ABL) gene. Translation of this transcript results in a chimeric BCR–ABL protein that possesses increased tyrosine kinase activity. Chimeric transcripts characterize specific cellular phenotypes and are suspected to function not only in cancer, but also in normal cells. One example of a chimera in normal human cells is generated by trans-splicing of the 5′ exons of the JAZF1 gene on chromosome 7p15 and the 3′ exons of JJAZ1 (SUZ12) on chromosome 17q1. This chimeric RNA is translated in endometrial stroma cells and encodes an anti-apoptotic protein. Notable examples of chimeric genes in cancer are the fused BCR-ABL, FUS-ERG, MLL-AF6, and MOZ-CBP genes expressed in acute myeloid leukemia (AML), and the TMPRSS2-ETS chimera associated with overexpression of the oncogene in prostate cancer. [1]

Characteristics of chimeric proteins

Frenkel-Morgenstern et al. have defined two main features of chimeric proteins. They have reported that chimeras exploit signal peptides and transmembrane domains to alter the cellular localization of the associated activities. Second, chimeras incorporate parental genes that are expressed at a high level. [1] A survey of all the functional domains in proteins encoded by chimeric transcripts demonstrated that chimeras contain complete protein domains significantly more often than in random data sets. [9] 0-==0

Databases of chimeric transcripts

Several databases have been constructed to incorporate chimeric transcripts from different resources using a variety of computational procedures:

Computational tools for detecting chimeric RNA

Recent advances in high throughput transcriptome sequencing have paved the way for new computational methods for fusion discovery. The following are computational tools available for detection of fusion transcripts from RNA-Seq data:

Some caution needs to be applied in the interpretation of trans-splicing events detected in high-throughput sequencing experiments as the reverse transcriptase enzymes ubiquitously used to determine RNA sequences are capable of introducing apparent trans-splicing events that were not present in the original RNA. [26] [27] Some chimeric RNAs have been confirmed by other methods however. [28]

Chimeric RNA in lower eukaryotes

Although rare in higher eukaryotes, various lower eukaryotes including nematodes and trypanosomes make extensive use of trans-splicing to generate chimeric RNAs. [29] [30] In these organisms, splicing reactions between a protein coding RNA and a universal sequence result in the attachment of a splice-leader to the 5' end of the RNA, generating a functional messenger RNA. This system allows the use of operons - collections of protein-coding genes with a shared function that are simultaneously transcribed into a single RNA and then spliced into individual messenger RNAs, each of which codes for a single protein.

Related Research Articles

Exon Gene portion that is not removed during RNA splicing and becomes part of mature mRNA

An exon is any part of a gene that will encode 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 messenger RNA. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome.

RNA splicing Processing primary RNA to remove intron sequences and join the remaining exon sections

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 introns and so joining 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.

Human genome Complete set of nucleic acid sequences for humans

The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome. Human genomes include both protein-coding DNA genes and noncoding DNA. Haploid human genomes, which are contained in germ cells consist of three billion DNA base pairs, while diploid genomes have twice the DNA content. While there are significant differences among the genomes of human individuals, these are considerably smaller than the differences between humans and their closest living relatives, the bonobos and chimpanzees.

Alternative splicing Process by which a single gene can code for multiple proteins

Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions. Notably, alternative splicing allows the human genome to direct the synthesis of many more proteins than would be expected from its 20,000 protein-coding genes.

In computational biology, gene prediction or gene finding refers to the process of identifying the regions of genomic DNA that encode genes. This includes protein-coding genes as well as RNA genes, but may also include prediction of other functional elements such as regulatory regions. Gene finding is one of the first and most important steps in understanding the genome of a species once it has been sequenced.

Trans-splicing is a special form of RNA processing where exons from two different primary RNA transcripts are joined end to end and ligated. It is usually found in eukaryotes and mediated by the spliceosome, although some bacteria and archaea also have "half-genes" for tRNAs.

Fusion gene

A fusion gene is a hybrid gene formed from two previously independent genes. It can occur as a result of translocation, interstitial deletion, or chromosomal inversion. Fusion genes have been found to be prevalent in all main types of human neoplasia. The identification of these fusion genes play a prominent role in being a diagnostic and prognostic marker.

<i>ERG</i> (gene)

ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

RBM9

RNA binding motif protein 9 (RBM9), also known as Rbfox2, is a protein which in humans is encoded by the RBM9 gene.

POLR2J2

DNA directed RNA polymerase II polypeptide J-related gene, also known as POLR2J2, is a human gene.

RNA-Seq Lab technique in cellular biology

RNA-Seq is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing cellular transcriptome.

In genetics and molecular biology, a chimera is a single DNA sequence originating from multiple transcripts or parent sequences. It can occur in various contexts. Chimeras are generally considered a contaminant, as a chimera can be interpreted as a novel sequence while it is in fact an artifact. However, the formation of artificial chimeras can also be a useful tool in the molecular biology. For example, in protein engineering, "chimeragenesis " is one of the "two major techniques used to manipulate cDNA sequences".

Periannan Senapathy is a molecular biologist, geneticist, author and entrepreneur. He is the founder, president and chief scientific officer at Genome International Corporation, a biotechnology, bioinformatics, and information technology firm based in Madison, Wisconsin, which develops computational genomics applications of next-generation DNA sequencing (NGS) and clinical decision support systems for analyzing patient genome data that aids in diagnosis and treatment of diseases.

De novo transcriptome assembly is the de novo sequence assembly method of creating a transcriptome without the aid of a reference genome.

Circular RNA Type of RNA found in cells

Circular RNA is a type of single-stranded RNA which, unlike linear RNA, forms a covalently closed continuous loop. In circular RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together. This feature confers numerous properties to circular RNA, many of which have only recently been identified.

Uncharacterized protein C2orf27 is a protein that in humans is encoded by the C2orf27A gene. Although its function is not clearly understood, through the use of bioinformatic analysis more information is being brought to light.

TopHat is an open-source bioinformatics tool for the throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies using Bowtie first and then mapping to a reference genome to discover RNA splice sites de novo. TopHat aligns RNA-Seq reads to mammalian-sized genomes.

In molecular phylogenetics, relationships among individuals are determined using character traits, such as DNA, RNA or protein, which may be obtained using a variety of sequencing technologies. High-throughput next-generation sequencing has become a popular technique in transcriptomics, which represent a snapshot of gene expression. In eukaryotes, making phylogenetic inferences using RNA is complicated by alternative splicing, which produces multiple transcripts from a single gene. As such, a variety of approaches may be used to improve phylogenetic inference using transcriptomic data obtained from RNA-Seq and processed using computational phylogenetics.

Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. Here, mRNA serves as a transient intermediary molecule in the information network, whilst non-coding RNAs perform additional diverse functions. A transcriptome captures a snapshot in time of the total transcripts present in a cell. Transcriptomics technologies provide a broad account of which cellular processes are active and which are dormant. A major challenge in molecular biology lies in understanding how the same genome can give rise to different cell types and how gene expression is regulated.

References

  1. 1 2 3 4 5 Frenkel-Morgenstern, M.; Lacroix, V.; Ezkurdia, I.; Levin, Y.; Gabashvili, A.; Prilusky, J.; del Pozo, A.; Tress, M.; Johnson, R.; Guigo, R.; Valencia, A. (15 May 2012). "Chimeras taking shape: Potential functions of proteins encoded by chimeric RNA transcripts". Genome Research. 22 (7): 1231–1242. doi:10.1101/gr.130062.111. PMC   3396365 . PMID   22588898.
  2. ↑ Horspool, Daniel (2008-11-28). "Central Dogma of Molecular Biochemistry with Enzymes" . Retrieved 22 July 2013.
  3. ↑ CRICK, FRANCIS (August 1970). "Central Dogma of Molecular Biology". Nature. 227 (5258): 561–563. Bibcode:1970Natur.227..561C. doi:10.1038/227561a0. PMID   4913914. S2CID   4164029.
  4. ↑ Geer, R.C. "Introduction to Molecular Biology Resources" . Retrieved 22 July 2013.
  5. 1 2 3 James D. Watson; et al. (2007). Molecular biology of the gene (6th ed.). San Francisco, Calif.: Benjamin Cummings. ISBN   9780805395921.
  6. ↑ Tomlins, SA; Mehra, R; Rhodes, DR; Smith, LR; Roulston, D; Helgeson, BE; Cao, X; Wei, JT; Rubin, MA; Shah, RB; Chinnaiyan, AM (Apr 1, 2006). "TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer". Cancer Research. 66 (7): 3396–400. doi: 10.1158/0008-5472.CAN-06-0168 . PMID   16585160.
  7. ↑ Panagopoulos, Ioannis; Thorsen, Jim; Gorunova, Ludmila; Micci, Francesca; Haugom, Lisbeth; Davidson, Ben; Heim, Sverre (1 August 2013). "RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14;22)(q32;q12)". Genes, Chromosomes and Cancer. 52 (8): 733–740. doi:10.1002/gcc.22068. PMID   23630070. S2CID   28377909.
  8. ↑ Koontz, J. I.; Soreng, A. L.; Nucci, M.; Kuo, F. C.; Pauwels, P.; van den Berghe, H.; Cin, P. D.; Fletcher, J. A.; Sklar, J. (22 May 2001). "Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors". Proceedings of the National Academy of Sciences. 98 (11): 6348–6353. Bibcode:2001PNAS...98.6348K. doi: 10.1073/pnas.101132598 . PMC   33471 . PMID   11371647.
  9. ↑ Frenkel-Morgenstern, M.; Valencia, A. (11 June 2012). "Novel domain combinations in proteins encoded by chimeric transcripts". Bioinformatics. 28 (12): i67–i74. doi:10.1093/bioinformatics/bts216. PMC   3371848 . PMID   22689780.
  10. ↑ Gorohovski, A.; Tagore, S.; Palande, V.; Malka, A.; Raviv-Shay, D.; Frenkel-Morgenstern, M. (4 January 2017). "ChiTaRS-3.1—the enhanced chimeric transcripts and RNA-seq database matched with protein–protein interactions". Nucleic Acids Research. 45 (D1): D790–D795. doi:10.1093/nar/gkw1127. PMC   5210585 . PMID   27899596.
  11. ↑ Frenkel-Morgenstern, M.; Gorohovski, A.; Vucenovic, D.; Maestre, L.; Valencia, A. (28 January 2015). "ChiTaRS 2.1--an improved database of the chimeric transcripts and RNA-seq data with novel sense-antisense chimeric RNA transcripts". Nucleic Acids Research. 43 (D1): D68–D75. doi:10.1093/nar/gku1199. PMC   4383979 . PMID   25414346.
  12. ↑ Frenkel-Morgenstern, M.; Gorohovski, A.; Lacroix, V.; Rogers, M.; Ibanez, K.; Boullosa, C.; Andres Leon, E.; Ben-Hur, A.; Valencia, A. (9 November 2012). "ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data". Nucleic Acids Research. 41 (D1): D142–D151. doi:10.1093/nar/gks1041. PMC   3531201 . PMID   23143107.
  13. ↑ Kim, P.; Yoon, S.; Kim, N.; Lee, S.; Ko, M.; Lee, H.; Kang, H.; Kim, J.; Lee, S. (11 November 2009). "ChimerDB 2.0--a knowledgebase for fusion genes updated". Nucleic Acids Research. 38 (Database): D81–D85. doi:10.1093/nar/gkp982. PMC   2808913 . PMID   19906715.
  14. ↑ Kim, Dae-Soo; Huh, Jae-Won; Kim, Heui-Soo (1 January 2007). "HYBRIDdb: a database of hybrid genes in the human genome". BMC Genomics. 8 (1): 128. doi:10.1186/1471-2164-8-128. PMC   1890557 . PMID   17519042.
  15. ↑ Novo, FJ; de Mendíbil, IO; Vizmanos, JL (Jan 26, 2007). "TICdb: a collection of gene-mapped translocation breakpoints in cancer". BMC Genomics. 8: 33. doi:10.1186/1471-2164-8-33. PMC   1794234 . PMID   17257420.
  16. ↑ Kong, F.; Zhu, J.; Wu, J.; Peng, J.; Wang, Y.; Wang, Q.; Fu, S.; Yuan, L.-L.; Li, T. (4 November 2010). "dbCRID: a database of chromosomal rearrangements in human diseases". Nucleic Acids Research. 39 (Database): D895–D900. doi:10.1093/nar/gkq1038. PMC   3013658 . PMID   21051346.
  17. ↑ Bruno, Andrew; Jeffrey C Miecznikowski; Maochun Qin; Jianmin Wang; Song Liu (January 2013). "FUSIM: a Software Tool for Simulating Fusion Transcripts". BMC Bioinformatics. 14 (13): 13. doi:10.1186/1471-2105-14-13. PMC   3637076 . PMID   23323884.
  18. ↑ Philippe, Nicolas; Salson, Mikaël; Commes, Thérèse; Rivals, Eric (1 January 2013). "CRAC: an integrated approach to the analysis of RNA-seq reads". Genome Biology. 14 (3): R30. doi:10.1186/gb-2013-14-3-r30. PMC   4053775 . PMID   23537109.
  19. ↑ Kim, Daehwan; Salzberg, Steven L (1 January 2011). "TopHat-Fusion: an algorithm for discovery of novel fusion transcripts". Genome Biology. 12 (8): R72. doi:10.1186/gb-2011-12-8-r72. PMC   3245612 . PMID   21835007.
  20. ↑ Piazza, R.; Pirola, A.; Spinelli, R.; Valletta, S.; Redaelli, S.; Magistroni, V.; Gambacorti-Passerini, C. (8 May 2012). "FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery". Nucleic Acids Research. 40 (16): e123. doi:10.1093/nar/gks394. PMC   3439881 . PMID   22570408.
  21. ↑ Iyer, M. K.; Chinnaiyan, A. M.; Maher, C. A. (11 August 2011). "ChimeraScan: a tool for identifying chimeric transcription in sequencing data". Bioinformatics. 27 (20): 2903–2904. doi:10.1093/bioinformatics/btr467. PMC   3187648 . PMID   21840877.
  22. ↑ Li, Y.; Chien, J.; Smith, D. I.; Ma, J. (5 May 2011). "FusionHunter: identifying fusion transcripts in cancer using paired-end RNA-seq". Bioinformatics. 27 (12): 1708–1710. doi: 10.1093/bioinformatics/btr265 . PMID   21546395.
  23. ↑ Ameur, Adam; Wetterbom, Anna; Feuk, Lars; Gyllensten, Ulf (1 January 2010). "Global and unbiased detection of splice junctions from RNA-seq data". Genome Biology. 11 (3): R34. doi:10.1186/gb-2010-11-3-r34. PMC   2864574 . PMID   20236510.
  24. ↑ Robertson, Gordon; Schein, Jacqueline; Chiu, Readman; Corbett, Richard; Field, Matthew; Jackman, Shaun D; Mungall, Karen; Lee, Sam; Okada, Hisanaga Mark; Qian, Jenny Q; Griffith, Malachi; Raymond, Anthony; Thiessen, Nina; Cezard, Timothee; Butterfield, Yaron S; Newsome, Richard; Chan, Simon K; She, Rong; Varhol, Richard; Kamoh, Baljit; Prabhu, Anna-Liisa; Tam, Angela; Zhao, YongJun; Moore, Richard A; Hirst, Martin; Marra, Marco A; Jones, Steven J M; Hoodless, Pamela A; Birol, Inanc (10 October 2010). "De novo assembly and analysis of RNA-seq data". Nature Methods. 7 (11): 909–912. doi:10.1038/nmeth.1517. PMID   20935650. S2CID   1034682.
  25. ↑ Sboner, Andrea; Habegger, Lukas; Pflueger, Dorothee; Terry, Stephane; Chen, David Z; Rozowsky, Joel S; Tewari, Ashutosh K; Kitabayashi, Naoki; Moss, Benjamin J; Chee, Mark S; Demichelis, Francesca; Rubin, Mark A; Gerstein, Mark B (1 January 2010). "FusionSeq: a modular framework for finding gene fusions by analyzing Paired-End RNA-Sequencing data". Genome Biology. 11 (10): R104. doi:10.1186/gb-2010-11-10-r104. PMC   3218660 . PMID   20964841.
  26. ↑ Houseley, J; Tollervey, D (Aug 18, 2010). "Apparent non-canonical trans-splicing is generated by reverse transcriptase in vitro". PLOS ONE. 5 (8): e12271. Bibcode:2010PLoSO...512271H. doi: 10.1371/journal.pone.0012271 . PMC   2923612 . PMID   20805885.
  27. ↑ McManus, CJ; Duff, MO; Eipper-Mains, J; Graveley, BR (Jul 20, 2010). "Global analysis of trans-splicing in Drosophila". Proceedings of the National Academy of Sciences of the United States of America. 107 (29): 12975–9. Bibcode:2010PNAS..10712975M. doi: 10.1073/pnas.1007586107 . PMC   2919919 . PMID   20615941.
  28. ↑ Djebali, S; Lagarde, J; Kapranov, P; Lacroix, V; Borel, C; Mudge, JM; Howald, C; Foissac, S; Ucla, C; Chrast, J; Ribeca, P; Martin, D; Murray, RR; Yang, X; Ghamsari, L; Lin, C; Bell, I; Dumais, E; Drenkow, J; Tress, ML; Gelpí, JL; Orozco, M; Valencia, A; van Berkum, NL; Lajoie, BR; Vidal, M; Stamatoyannopoulos, J; Batut, P; Dobin, A; Harrow, J; Hubbard, T; Dekker, J; Frankish, A; Salehi-Ashtiani, K; Reymond, A; Antonarakis, SE; Guigó, R; Gingeras, TR (2012). "Evidence for transcript networks composed of chimeric RNAs in human cells". PLOS ONE. 7 (1): e28213. Bibcode:2012PLoSO...728213D. doi: 10.1371/journal.pone.0028213 . PMC   3251577 . PMID   22238572.
  29. ↑ Blumenthal, T (Jun 25, 2005). "Trans-splicing and operons". WormBook: 1–9. doi: 10.1895/wormbook.1.5.1 . PMID   18050426.
  30. ↑ Michaeli, S (Apr 2011). "Trans-splicing in trypanosomes: machinery and its impact on the parasite transcriptome". Future Microbiology. 6 (4): 459–74. doi:10.2217/fmb.11.20. PMID   21526946.
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.