RNA binding proteins (RBPs) regulate lncRNA nuclear retention

It is well known that functional modes of lncRNAs are intimately associated with their subcellular localization1 and relative nuclear enrichment of lncRNAs compared to mRNAs is a prevalent phenomenon2. As RBPs control the production, maturation, localization, translation, and degradation of cellular RNAs3, we reason that it is important to uncover partner RBPs that can bind and facilitate lncRNA nuclear localization. In this study, we thus harnessed the recently released large scale of eCLIP data4 and subcellular RNA-seq data5 available in K562 and HepG2 cell lines to characterize lncRNA-RBP interactome and uncovered potential factors and associated mechanisms determining lncRNA nuclear retention. Analyses of the subcellular RNA-seq data identified nuclear enriched lncRNAs (nuc-lncRNAs) and confirmed that lncRNAs and eRNAs (enhancer associated lncRNAs) are relatively nuclear enriched in both cells. By integrating the RBP binding profiles, we next generated RBP/nuc-lncRNA interaction map to identify RBPs associated with nuc-lncRNAs including HNRNPU, SAFB2, KHSRP and KHDRBS1 in K562 and HRNPNPC as well as HNRNPL in HepG2 cell lines. To further confirm the above findings, HNRNPU was knocked down and which led to nuclear retention of a panel of lncRNAs.