title: In Vivo Mapping of Eukaryotic RNA Interactomes Reveals Principles of Higher-Order Organization and Regulation.
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.
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Jong Ghut Ashley
authors.initials: JG
authors.lastname: Aw
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wilm
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Xin Ni
authors.initials: XN
authors.lastname: Lim
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Kum-Loong
authors.initials: KL
authors.lastname: Boon
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Sidika
authors.initials: S
authors.lastname: Tapsin
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Yun-Shen
authors.initials: YS
authors.lastname: Chan
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Cheng-Peow
authors.initials: CP
authors.lastname: Tan
authors.affiliation: Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street #07-01, Matrix 138671, Singapore.
authors.forename: Adelene Y L
authors.initials: AY
authors.lastname: Sim
authors.affiliation: Human Genetics, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Teodorus Theo
authors.initials: TT
authors.lastname: Susanto
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore. Electronic address: nagarajann@gis.a-star.edu.sg.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
authors.affiliation: Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore. Electronic address: wany@gis.a-star.edu.sg.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wan
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation; D019295:Computational Biology; D003432:Cross-Linking Reagents / Q000737:chemistry; D030541:Databases, Genetic; D053595:Embryonic Stem Cells / Q000378:metabolism; D005363:Ficusin / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D003432:Cross-Linking Reagents; D012331:RNA, Fungal; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; D005363:Ficusin