Tumor-associated intronic editing of HNRPLL generates a novel splicing variant linked to cell proliferation

The Journal of Biological Chemistry
Yi-Tung ChenBertrand Chin-Ming Tan

Abstract

Processing of the eukaryotic transcriptome is a dynamic regulatory mechanism that confers genetic diversity, and splicing and adenosine to inosine (A-to-I) RNA editing are well-characterized examples of such processing. Growing evidence reveals the cross-talk between the splicing and RNA editing, but there is a paucity of substantial evidence for its mechanistic details and contribution in a physiological context. Here, our findings demonstrate that tumor-associated differential RNA editing, in conjunction with splicing machinery, regulates the expression of variants of HNRPLL, a gene encoding splicing factor. We discovered an HNRPLL transcript variant containing an additional exon 12A (E12A), which is a substrate of ADAR1 and ADAR2. Adenosine deaminases acting on RNA (ADAR) direct deaminase-dependent expression of the E12A transcript, and ADAR-mediated regulation of E12A is largely splicing-based, and does not affect the stability or nucleocytoplasmic distribution of the transcript. Furthermore, ADAR-mediated modification of exon 12A generates an enhancer for the oncogenic splicing factor SRSF1 and consequently promotes the frequency of alternative splicing. Gene expression profiling by RNA-seq revealed that E12A acts distinct...Continue Reading

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Citations

Jan 9, 2019·Frontiers in Endocrinology·Che-Pei KungJason D Weber
Feb 6, 2020·Molecular Medicine Reports·Xiang WangZhijie Xu
Jul 28, 2020·International Journal of Molecular Sciences·Katarzyna Taylor, Krzysztof Sobczak
Feb 7, 2020·Nature Communications·Leonidas SalichosMark Gerstein

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