RNA-Regulated TRA-1 nuclear export controls sexual fate

Area of Science:

• Developmental biology
• Molecular genetics
• RNA biology

Background:

• TRA-1, a GLI family transcription factor, is essential for female development in C. elegans.
• Sex-specific differences in TRA-1 localization suggest a regulatory mechanism controlling its activity.

Purpose of the Study:

• To investigate the mechanisms regulating TRA-1 localization and activity in C. elegans.
• To elucidate the role of TRA-2 mRNA in controlling TRA-1 nuclear export and function.

Main Methods:

• Sex-specific localization analysis of TRA-1 in C. elegans.
• Treatment with leptomycin B, a CRM1-dependent export inhibitor.
• Analysis of TRA-1 binding to the tra-2 3' untranslated region (UTR).

Main Results:

• Nuclear TRA-1 levels are higher in hermaphrodites than in males, particularly in the intestine and germline.
• Inhibition of nuclear export by leptomycin B increases nuclear TRA-1 in males.
• Disruption of TRA-1 binding to tra-2 3' UTR increases nuclear TRA-1 and promotes female development.
• Evidence suggests coexport of a TRA-1/tra-2 mRNA complex reduces TRA-1 nuclear activity.

Conclusions:

• TRA-1 nuclear export is a key regulatory step in C. elegans female development.
• TRA-1 binding to tra-2 mRNA facilitates its nuclear export, thereby modulating its transcriptional activity.
• This study reveals an RNA-based mechanism controlling transcription factor activity and cell fate determination.