Sharing the load: Mex67-Mtr2 cofunctions with Los1 in primary tRNA nuclear export

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Eukaryotic transfer RNAs (tRNAs) are synthesized in the nucleus and exported to the cytoplasm for protein synthesis.
• Los1 (Exportin-t) was the sole known nuclear exporter for intron-containing pre-tRNAs, despite its non-essential nature.
• The essential process of tRNA nuclear export necessitates the identification of all involved factors.

Purpose of the Study:

• To identify novel factors involved in essential tRNA nuclear export.
• To elucidate the role of the Mex67-Mtr2 complex in tRNA nuclear export.
• To investigate the functional relationship between Los1 and Mex67-Mtr2 in tRNA export.

Main Methods:

• Molecular, genetic, cytological, and biochemical analyses in budding yeast.
• Inactivation and overexpression studies of Mex67 and Mtr2.
• In vivo coimmunoprecipitation assays to detect Mex67-tRNA interactions.

Main Results:

• The Mex67-Mtr2 heterodimer cofunctions with Los1 in nuclear export of intron-containing pre-tRNAs.
• Inactivation of Mex67 or Mtr2 causes accumulation of unspliced tRNAs in the nucleus.
• Overexpression of Mex67-Mtr2 can compensate for Los1 deficiency, and Mex67 binds tRNAs.

Conclusions:

• Mex67-Mtr2 is a key component in the primary nuclear export pathway for a subset of yeast tRNAs.
• The discovery of Mex67-Mtr2 in tRNA export expands our understanding of nuclear export mechanisms.
• Differential tRNA substrate preferences among exporters suggest a regulatory role for tRNA nuclear export in proteome control.