The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
The RNA-binding protein hnRNPLL induces a T cell alternative splicing program delineated by differential intron retention in polyadenylated RNA
Open accessAbstract
Background: Retention of a subset of introns in spliced polyadenylated mRNA is emerging as a frequent, unexplained finding from RNA deep sequencing in mammalian cells. Results: Here we analyze intron retention in T lymphocytes by deep sequencing polyadenylated RNA. We show a developmentally regulated RNA-binding protein, hnRNPLL, induces retention of specific introns by sequencing RNA from T cells with an inactivating Hnrpll mutation and from B lymphocytes that physiologically downregulate Hnrpll during their differentiation. In Ptprc mRNA encoding the tyrosine phosphatase CD45, hnRNPLL induces selective retention of introns flanking exons 4 to 6; these correspond to the cassette exons containing hnRNPLL binding sites that are skipped in cells with normal, but not mutant or low, hnRNPLL. We identify similar patterns of hnRNPLL-induced differential intron retention flanking alternative exons in 14 other genes, representing novel elements of the hnRNPLL-induced splicing program in T cells. Retroviral expression of a normally spliced cDNA for one of these targets, Senp2, partially corrects the survival defect of Hnrpll-mutant T cells. We find that integrating a number of computational methods to detect genes with differentially retained introns provides a strategy to enrich for alternatively spliced exons in mammalian RNA-seq data, when complemented by RNA-seq analysis of purified cells with experimentally perturbed RNA-binding proteins. Conclusions: Our findings demonstrate that intron retention in mRNA is induced by specific RNA-binding proteins and suggest a biological significance for this process in marking exons that are poised for alternative splicing.
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Metadata
- Authors
- Cho, V., Mei, Y., Sanny, A., Chan, S., Enders, A., Bertram, E. M., Tan, A., Goodnow, C. C., & Andrews, T. D.
- Venue
- Genome Biology
- Published
- 2014-01-29
- Volume
- 15
- Issue
- 1
- Pages
- R26-R26
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- OpenAlex
- W2129497875
- Cited by
- 339
- References
- 41
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- gold
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- Cho, V., Mei, Y., Sanny, A., Chan, S., Enders, A., Bertram, E. M., Tan, A., Goodnow, C. C., & Andrews, T. D. (2014). The RNA-binding protein hnRNPLL induces a T cell alternative splicing program delineated by differential intron retention in polyadenylated RNA. Genome Biology. https://doi.org/10.1186/gb-2014-15-1-r26
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