Do non-genomically encoded fusion transcripts cause recurrent chromosomal translocations?
- We among others have recently demonstrated that normal cells produce “fusion mRNAs”. These fusion mRNAs do not derive from rearranged genomic loci, but rather they are derived from “early-terminated transcripts” (ETTs). Premature transcriptional termination takes place in intronic sequences that belong to “breakpoint cluster regions”. One important property of ETTs is that they exhibit an unsaturated splice donor site. This results in: (1) splicing to “cryptic exons” present in the final intron; (2) Splicing to another transcript of the same gene (intragenic trans-splicing), resulting in “exon repetitions”; (3) splicing to a transcript of another gene (intergenic trans-splicing), leading to “non-genomically encoded fusion transcripts” (NGEFTs). These NGEFTs bear the potential risk to influence DNA repair processes, since they share identical nucleotides with their DNA of origin, and thus, could be used as “guidance RNA” for DNA repair processes. Here, we present experimental data about four other genes. Three of them are associated with hemato-malignancies (ETV6, NUP98 and RUNX1), while one is associated with solid tumors (EWSR1). Our results demonstrate that all genes investigated so far (MLL, AF4, AF9, ENL, ELL, ETV6, NUP98, RUNX1 and EWSR1) display ETTs and produce transpliced mRNA species, indicating that this is a genuine property of translocating genes.
Author: | Eric KowarzORCiDGND, Theodor DingermannORCiDGND, Rolf MarschalekORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-300113 |
DOI: | https://doi.org/10.3390/cancers4041036 |
ISSN: | 2072-6694 |
Parent Title (English): | Cancers |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2013/05/23 |
Date of first Publication: | 2012/10/18 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2013/05/23 |
Tag: | RNA-templated DNA repair; genetic rearrangements; leukemia; solid tumors; premature transcript termination; recurrent chromosomal translocations |
Volume: | 4 |
Issue: | 4 |
Page Number: | 14 |
First Page: | 1036 |
Last Page: | 1049 |
Note: | © 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
HeBIS-PPN: | 346677580 |
Institutes: | Biochemie, Chemie und Pharmazie / Pharmazie |
Medizin / Medizin | |
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) | |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 3.0 |