A Short Tandem Repeat-Enriched RNA Assembles a Nuclear Compartment to Control Alternative Splicing and Promote Cell Survival

Karen Yap, Svetlana Mukhina, Gen Zhang, Jason S.C. Tan, Hong Sheng Ong, Eugene V. Makeyev

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)
130 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)525-540
Number of pages16
JournalMOLECULAR CELL
Volume72
Issue number3
Early online date11 Oct 2018
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • alternative splicing
  • cancer
  • cell survival
  • cell transformation
  • long noncoding RNA
  • nuclear body
  • perinucleolar compartment
  • PTBP1
  • RNA-binding protein
  • short tandem repeats

Fingerprint

Dive into the research topics of 'A Short Tandem Repeat-Enriched RNA Assembles a Nuclear Compartment to Control Alternative Splicing and Promote Cell Survival'. Together they form a unique fingerprint.

Cite this