期刊
MOLECULAR CELL
卷 72, 期 3, 页码 525-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2018.08.041
关键词
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资金
- Biotechnology and Biological Sciences Research Council [BB/M007103/1, BB/R001049/1]
- European Commission (H2020-MSCA-RISE-2016) [734791]
- National Medical Research Council [NMRC/CBRG/0028/2013]
- BBSRC [BB/M007103/1, BB/R001049/1] Funding Source: UKRI
- Marie Curie Actions (MSCA) [734791] Funding Source: Marie Curie Actions (MSCA)
Functions of many long noncoding RNAs (lncRNAs) depend on their ability to interact with multiple copies of specific RNA-binding proteins (RBPs). Here, we devised a workflow combining bioinformatics and experimental validation steps to systematically identify RNAs capable of multivalent RBP recruitment. This uncovered a number of previously unknown transcripts encoding high-density RBP recognition arrays within genetically normal short tandem repeats. We show that a top-scoring hit in this screen, lncRNA PNCTR, contains hundreds of pyrimidine tract-binding protein (PTBP1)-specific motifs allowing it to sequester a substantial fraction of PTBP1 in a nuclear body called perinucleolar compartment. Importantly, PNCTR is markedly over-expressed in a variety of cancer cells and its downregulation is sufficient to induce programmed cell death at least in part by stimulating PTBP1 splicing regulation activity. This work expands our understanding of the repeat-containing fraction of the human genome and illuminates a novel mechanism driving malignant transformation of cancer cells.
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