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Mol Cell. 2016 May 19;62(4):603-17. doi: 10.1016/j.molcel.2016.04.028. Epub 2016 May 12.

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

Author information

1
Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
2
Computational and Systems Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
3
Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street #07-01, Matrix 138671, Singapore.
4
Human Genetics, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
5
Computational and Systems Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore. Electronic address: nagarajann@gis.a-star.edu.sg.
6
Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore. Electronic address: wany@gis.a-star.edu.sg.

Abstract

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, ligated, 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 underexplored complexity of RNA interactomes and pave the way to better understanding how RNA organization impacts biology.

PMID:
27184079
DOI:
10.1016/j.molcel.2016.04.028
[Indexed for MEDLINE]
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