Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/87602
Title: A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival
Authors: Tan, Jason S. C.
Yap, Karen
Mukhina, Svetlana
Zhang, Gen
Ong, Hong Sheng
Makeyev, Eugene V.
Keywords: Long Noncoding RNA
Short Tandem Repeats
Science::Biological sciences
Issue Date: 2018
Source: Yap, K., Mukhina, S., Zhang, G., Tan, J. S. C., Ong, H. S., & Makeyev, E. V. (2018). A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survivall. Molecular Cell, 72(3), 525-540. doi:10.1016/j.molcel.2018.08.041
Series/Report no.: Molecular Cell
Abstract: 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 overexpressed 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.
URI: https://hdl.handle.net/10356/87602
http://hdl.handle.net/10220/50329
ISSN: 1097-2765
DOI: http://dx.doi.org/10.1016/j.molcel.2018.08.041
Rights: © 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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