In Vivo Mapping of Eukaryotic RNA Interactomes Reveals Principles of Higher-Order Organization and Regulation

Aw J. G. A. , Shen Y., Wilm A., Sun M., Lim X. N. , Boon K., ...More

MOLECULAR CELL, vol.62, no.4, pp.603-617, 2016 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 62 Issue: 4
  • Publication Date: 2016
  • Doi Number: 10.1016/j.molcel.2016.04.028
  • Journal Name: MOLECULAR CELL
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.603-617


Identifying pairwise RNA-RNA interactions is key to understanding how RNAs fold and interact with other RNAs inside the cell. We present a high-throughput approach, sequencing of psoralen crosslinked, /igated, and selected hybrids (SPLASH), that maps pairwise RNA interactions in vivo with high sensitivity and specificity, genome-wide. Applying SPLASH to human and yeast transcriptomes revealed the diversity and dynamics of thousands of long-range intra-and intermolecular RNA-RNA interactions. Our analysis highlighted key structural features of RNA classes, including the modular organization of mRNAs, its impact on translation and decay, and the enrichment of long-range interactions in noncoding RNAs. Additionally, intermolecular mRNA interactions were organized into network clusters and were remodeled during cellular differentiation. We also identified hundreds of known and new snoRNA-rRNA binding sites, expanding our knowledge of rRNA biogenesis. These results highlight the under-explored complexity of RNA interactomes and pave the way to better understanding how RNA organization impacts biology.