4 years ago

Dynamic landscape and regulation of RNA editing in mammals

Dynamic landscape and regulation of RNA editing in mammals
Amy N. Young, Jin Billy Li, Raghuvaran Shanmugam, Rui Zhang, Qin Li, Gokul Ramaswami, Dena S. Leeman, Jennefer Kohler, Avinash Ramu, Cyril X. George, Ajay Chawla, Gary Peltz, Alessandra Rustighi, Anne Brunet, Kentaro Ariyoshi, Carl R. Walkley, Elizabeth A. Pollina, Liam P. Keegan, Charles E. Samuel, Ni Huang, Ankita Gupte, Meng How Tan, Kazuko Nishikura, Kaiwen Ivy Liu, Robert Piskol, Mary A. O’Connell, Y. P. Sharon Goh, Donald F. Conrad, Giannino Del Sal
The prevalence and importance of A-to-I RNA editing have been illuminated in recent years largely owing to the rapid adoption of high-throughput sequencing technologies11, 12. Separate laboratories have examined the RNA editome across many tissues or developmental stages in human and other mammals13, 14, 15, 16, 17. However, the published studies are limited in the number of samples and tissues examined and do not systematically compare the editing landscape across species or thoroughly dissect the regulation of editing. In this work, we performed multidimensional analyses of thousands of new and publicly available sequencing libraries to address major gaps in our fundamental knowledge of A-to-I editing.

To construct a mammalian reference atlas of A-to-I editing, we first compiled a comprehensive list of editing sites in human and mouse (Supplementary Note 1) and then examined the RNA editome across tissues using 8,551 RNA-sequencing (RNA-seq) samples derived from 552 donors in the GTEx project (Supplementary Information 1). Notably, the editing profiles across different tissues were highly correlated (Fig. 1a) and the overall editing activities were also generally similar, except for skeletal muscle, in which editing was significantly lower than in other tissues (P < 2.2 × 10−16, Wilcoxon rank sum test; Fig. 1b). Nevertheless, principal component analysis (PCA) showed that the brain regions could still be resolved from non-brain tissues (Extended Data Fig. 1a). Within the brain, the cerebellum was clearly segregated from other brain parts (Extended Data Fig. 1b), possibly owing to higher expression of ADAR2 (also known as ADARB1) (Extended Data Fig. 1c). When we examined non-repetitive sites in coding regions only, the editing levels became more distinct among the various tissues (Fig. 1a). The different brain regions clustered together, as did heart and skeletal muscle. Unexpectedly, the artery was the most highly edited tissue type (Fig. 1c). The importance of RNA editing in vascular disease was demonstrated in a recent study18. We further validated the results obtained from the GTEx data by applying a targeted sequencing approach (microfluidics-based multiplex PCR and deep sequencing; mmPCR–seq)19 (Supplementary Note 2) to examine 1

-Abstract Truncated-

Publisher URL: http://dx.doi.org/10.1038/nature24041

DOI: 10.1038/nature24041

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.