Maf1 protein, repressor of RNA polymerase III, indirectly affects tRNA processing

Area of Science:

• Molecular Biology
• Yeast Genetics
• RNA Polymerase III Regulation

Background:

• Maf1 is a known negative regulator of RNA polymerase III (Pol III) transcription in yeast.
• RNA polymerase III transcribes genes encoding small RNAs, including transfer RNAs (tRNAs).
• Proper tRNA biogenesis involves transcription, processing, and nuclear export.

Purpose of the Study:

• To investigate the role of Maf1 in tRNA biogenesis beyond its transcriptional regulatory function.
• To elucidate the mechanisms behind pre-tRNA accumulation observed in Maf1 deletion mutants.
• To understand the interplay between Maf1-mediated transcription control and tRNA nuclear export.

Main Methods:

• Analysis of pre-tRNA and mature tRNA levels in wild-type and maf1Δ yeast strains.
• Assessment of pre-tRNA accumulation under conditions of transcription inhibition.
• Investigation of the role of the tRNA exportin Los1 in pre-tRNA processing.

Main Results:

• Maf1 deletion (maf1Δ) leads to accumulation of primary transcripts and end-matured, intron-containing pre-tRNAs.
• Pre-tRNA accumulation in maf1Δ cells can be rescued by inhibiting transcription, suggesting processing machinery saturation.
• Saturation of the tRNA exportin Los1 contributes to the accumulation of end-matured pre-tRNAs in maf1Δ cells.
• Other tRNA processing components may also become limiting under conditions of increased tRNA transcription.

Conclusions:

• Maf1's role in tRNA biogenesis extends to coordinating transcription with processing and export.
• Increased tRNA transcription due to Maf1 loss saturates downstream processing and export pathways.
• Maf1-mediated transcription control and Los1-mediated nuclear export are coordinated regulatory steps in tRNA biosynthesis, responsive to environmental cues.