Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns
| Autor: | Catherine J. Wu, Eva Hrabeta-Robinson, Cameron M. Soulette, Angela N. Brooks, Kevyn Hart, Alison D. Tang, Marijke J. van Baren |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lymphoma RNA splicing Messenger General Physics and Astronomy medicine.disease_cause Genome informatics Transcriptome 0302 clinical medicine Cancer genomics Protein Isoforms Chronic lcsh:Science Cancer Genetics Mutation 0303 health sciences Multidisciplinary Leukemia High-throughput screening Hematology Lymphocytic 3. Good health 030220 oncology & carcinogenesis RNA Splicing Factors Gene isoform Adult Science Down-Regulation Bioengineering Genomics Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Rare Diseases Complementary DNA medicine Humans RNA Messenger Gene 030304 developmental biology Base Sequence Human Genome Alternative splicing Intron B-Cell RNA General Chemistry Phosphoproteins Leukemia Lymphocytic Chronic B-Cell Introns Alternative Splicing Nanopore Sequencing 030104 developmental biology lcsh:Q Nanopore sequencing RNA Splice Sites |
| Zdroj: | Nature communications, vol 11, iss 1 Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) |
| Popis: | While splicing changes caused by somatic mutations in SF3B1 are known, identifying full-length isoform changes may better elucidate the functional consequences of these mutations. We report nanopore sequencing of full-length cDNA from CLL samples with and without SF3B1 mutation, as well as normal B cell samples, giving a total of 149 million pass reads. We present FLAIR (Full-Length Alternative Isoform analysis of RNA), a computational workflow to identify high-confidence transcripts, perform differential splicing event analysis, and differential isoform analysis. Using nanopore reads, we demonstrate differential 3’ splice site changes associated with SF3B1 mutation, agreeing with previous studies. We also observe a strong downregulation of intron retention events associated with SF3B1 mutation. Full-length transcript analysis links multiple alternative splicing events together and allows for better estimates of the abundance of productive versus unproductive isoforms. Our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research. Long-read sequencing is useful in determining exon-connectivity of full-length mRNA isoforms. Here, by long-read nanopore sequencing, the authors report that intron retention is downregulated in SF3B1 mutant chronic lymphocytic leukemia cells than normal B cells. |
| Databáze: | OpenAIRE |
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