• search hit 1 of 3
Back to Result List

Direct long-read RNA sequencing identifies a subset of questionable exitrons likely arising from reverse transcription artifacts

  • Resistance to CD19-directed immunotherapies in lymphoblastic leukemia has been attributed, among other factors, to several aberrant CD19 pre-mRNA splicing events, including recently reported excision of a cryptic intron embedded within CD19 exon 2. While “exitrons” are known to exist in hundreds of human transcripts, we discovered, using reporter assays and direct long-read RNA sequencing (dRNA-seq), that the CD19 exitron is an artifact of reverse transcription. Extending our analysis to publicly available datasets, we identified dozens of questionable exitrons, dubbed “falsitrons,” that appear only in cDNA-seq, but never in dRNA-seq. Our results highlight the importance of dRNA-seq for transcript isoform validation.
Metadaten
Author:Laura SchulzGND, Manuel Torres-DizORCiD, Mariela Cortes LopezORCiDGND, Katharina E. HayerORCiDGND, Mukta AsnaniORCiD, Sarah K. TasianORCiD, Yoseph BarashORCiD, Elena SotilloORCiD, Katharina ZarnackORCiDGND, Julian KönigORCiDGND, Andrei Thomas-TikhonenkoORCiD
URN:urn:nbn:de:hebis:30:3-629833
DOI:https://doi.org/10.1186/s13059-021-02411-1
ISSN:1474-760X
Parent Title (English):Genome biology
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2021/06/28
Date of first Publication:2021/06/28
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/05/03
Tag:Alternative splicing; Blinatumomab; CD19; Exitrons; Immunotherapy; Long-read sequencing; Oxford Nanopore Technologies; Reverse transcription; mRNA isoforms
Volume:22
Issue:art. 190
Article Number:190
Page Number:12
First Page:1
Last Page:12
Note:
The results published here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.
Note:
Research in the ATT laboratory was supported by grants from the NIH (U01 CA232563), St. Baldrick’s-Stand Up to Cancer Pediatric Dream Team (SU2C-AACR-DT-27-17), the V Foundation for Cancer Research (T2018-014), and the Cookies for Kids’ Cancer (CFKC) Foundation.
Note:
Research in the KZ group and the JK laboratory was supported by grants from the German Research Foundation/Deutsche Forschungsgemeinschaft (ZA 881/2-1 and KO 4566/4-1, respectively).
HeBIS-PPN:508896258
Institutes:Biowissenschaften / Biowissenschaften
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International

OPUS4 Logo