SAM68 is required for regulation of Pumilio by the NORAD long noncoding RNA

Genes Dev. 2018 Jan 1;32(1):70-78. doi: 10.1101/gad.309138.117. Epub 2018 Jan 31.

Abstract

The number of known long noncoding RNA (lncRNA) functions is rapidly growing, but how those functions are encoded in their sequence and structure remains poorly understood. NORAD (noncoding RNA activated by DNA damage) is a recently characterized, abundant, and highly conserved lncRNA that is required for proper mitotic divisions in human cells. NORAD acts in the cytoplasm and antagonizes repressors from the Pumilio family that bind at least 17 sites spread through 12 repetitive units in NORAD sequence. Here we study conserved sequences in NORAD repeats, identify additional interacting partners, and characterize the interaction between NORAD and the RNA-binding protein SAM68 (KHDRBS1), which is required for NORAD function in antagonizing Pumilio. These interactions provide a paradigm for how repeated elements in a lncRNA facilitate function.

Keywords: NORAD; Pumilio; SAM68; long noncoding RNAs; post-transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adaptor Proteins, Signal Transducing / physiology
  • Binding Sites
  • Cell Line, Tumor
  • Chromosome Segregation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Gene Expression Regulation
  • Humans
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Long Noncoding / physiology
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • RNA-Binding Proteins / physiology
  • Repressor Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • KHDRBS1 protein, human
  • NORAD long non-coding RNA, human
  • PUM1 protein, human
  • PUM2 protein, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins