RBM33 directs the nuclear export of transcripts containing GC-rich elements

Anu Thomas, Frederick Rehfeld, He Zhang, Tsung-Cheng Chang, Mohammad Goodarzi, Frank Gillet, Joshua T. Mendell

Research output: Contribution to journalArticlepeer-review

Abstract

Although splicing is a major driver of RNA nuclear export, many intronless RNAs are efficiently exported to the cytoplasm through poorly characterized mechanisms. For example, GC-rich sequences promote nuclear export in a splicing-independent manner, but how GC content is recognized and coupled to nuclear export is unknown. Here, we developed a genome-wide screening strategy to investigate the mechanism of export of NORAD, an intronless cytoplasmic long noncoding RNA (lncRNA). This screen revealed an RNA binding protein, RBM33, that directs the nuclear export of NORAD and numerous other transcripts. RBM33 directly binds substrate transcripts and recruits components of the TREX–NXF1/NXT1 RNA export pathway. Interestingly, high GC content emerged as the feature that specifies RBM33-dependent nuclear export. Accordingly, RBM33 directly binds GC-rich elements in target transcripts. These results provide a broadly applicable strategy for the genetic dissection of nuclear export mechanisms and reveal a long-sought nuclear export pathway for transcripts with GC-rich sequences.

Original languageEnglish (US)
Pages (from-to)550-565
Number of pages16
JournalGenes and Development
Volume36
Issue number9-10
DOIs
StatePublished - May 1 2022

Keywords

  • GC content
  • GC-rich elements
  • lncRNAs
  • long noncoding RNAs
  • NORAD
  • nuclear export
  • RBM33

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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