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

Area of Science:

• Molecular Biology
• Genetics
• RNA Biology

Background:

• Splicing is a primary mechanism for RNA nuclear export.
• Intronless RNAs are exported via poorly understood pathways.
• GC-rich sequences are known to promote splicing-independent nuclear export.

Purpose of the Study:

• To investigate the mechanism of nuclear export for intronless RNAs, specifically the long noncoding RNA NORAD.
• To identify proteins involved in the splicing-independent nuclear export of GC-rich transcripts.

Main Methods:

• Developed a genome-wide screening strategy to identify factors involved in NORAD export.
• Utilized RNA binding protein assays to confirm direct binding of identified proteins to target RNAs.
• Investigated the recruitment of RNA export pathway components.

Main Results:

• Identified RBM33 as an RNA binding protein essential for the nuclear export of NORAD and other transcripts.
• RBM33 directly binds GC-rich elements within target RNA sequences.
• RBM33 recruits components of the TREX-NXF1/NXT1 RNA export pathway.

Conclusions:

• High GC content specifies RBM33-dependent nuclear export.
• Discovered a novel nuclear export pathway for GC-rich transcripts mediated by RBM33.
• The developed screening strategy is broadly applicable for dissecting RNA nuclear export mechanisms.