AI Article Synopsis
- - RNA editing and splicing are crucial processes that enhance the diversity of human transcripts, with ADAR1 being a key player linking the two, especially in relation to diseases like cancer.
- - The research identifies around a hundred key splicing events influenced by ADAR1 and ADAR2, demonstrating their ability to regulate exon selection in various ways.
- - The study reveals specific mechanisms by which ADAR proteins interact with double-stranded RNA to affect splicing, and these changes in splicing have direct implications for tumor development, rather than being side effects of RNA editing.
Article Abstract
RNA editing and splicing are the two major processes that dynamically regulate human transcriptome diversity. Despite growing evidence of crosstalk between RNA editing enzymes (mainly ADAR1) and splicing machineries, detailed mechanistic explanations and their biological importance in diseases, such as cancer are still lacking. Herein, we identify approximately a hundred high-confidence splicing events altered by ADAR1 and/or ADAR2, and ADAR1 or ADAR2 protein can regulate cassette exons in both directions. We unravel a binding tendency of ADARs to dsRNAs that involves GA-rich sequences for editing and splicing regulation. ADAR1 edits an intronic splicing silencer, leading to recruitment of SRSF7 and repression of exon inclusion. We also present a mechanism through which ADAR2 binds to dsRNA formed between GA-rich sequences and polypyrimidine (Py)-tract and precludes access of U2AF65 to 3' splice site. Furthermore, we find these ADARs-regulated splicing changes per se influence tumorigenesis, not merely byproducts of ADARs editing and binding.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005744 | PMC |
| http://dx.doi.org/10.1038/s41467-020-14621-5 | DOI Listing |
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