Maf1 Protein, Repressor of RNA Polymerase III, Indirectly Affects tRNA Processing

Abstract

Maf1 is negative regulator of RNA polymerase III in yeast. We observed high levels of both primary transcript and end-matured, intron-containing pre-tRNAs in the maf1⌬ strain. This pre-tRNA accumulation could be overcome by transcription inhibition, arguing against a direct role of Maf1 in tRNA maturation and suggesting saturation of processing machinery by the increased amounts of primary transcripts. Saturation of the tRNA exportin, Los1, is one reason why end-matured introncontaining pre-tRNAs accumulate in maf1⌬ cells. However, it is likely possible that other components of the processing pathway are also limiting when tRNA transcription is increased. According to our model, Maf1-mediated transcription control and nuclear export by Los1 are two major stages of tRNA biosynthesis that are regulated by environmental conditions in a coordinated manner.

Maf1-mediated repression of RNA polymerase III transcription inhibits tRNA degradation via RTD pathway

“…We have shown recently that Maf1 indirectly affects maturation of tRNA precursors (Karkusiewicz et al 2011). End-matured intron-containing pre-tRNAs accumulate in cells lacking Maf1 due to saturation of processing machinery by the increased amounts of primary transcripts.…”

“…In yeast, the end-processed tRNAs are transported to the cytoplasm where introns are removed (for review, see Phizicky and Hopper 2010). The nuclear export of yeast tRNA is regulated by environmental conditions in coordination with Maf1-mediated transcription control, thereby coupling tRNA synthesis and maturation (Karkusiewicz et al 2011).…”

Transfer RNA Post-Transcriptional Processing, Turnover, and Subcellular Dynamics in the YeastSaccharomyces cerevisiae

“…The level of tRNA available for translation is also regulated by tRNA nuclear export. In wild-type cells grown with a fermentable sugar as the carbon source, Los1 is located primarily in the nucleus where it is able to interact with newly synthesized tRNA cargo, but when cells are grown in a nonfermentable carbon source or when the cells are stressed, Los1 is primarily cytoplasmic and hence unable to access newly transcribed tRNAs and deliver them to the cytoplasm (Quan et al 2007;Karkusiewicz et al 2012). The subcellular distribution of Los1 is also affected by DNA damage.…”

“…Upon DNA damage, Los1 is primarily cytoplasmic (Ghavidel et al 2007). Cytoplasmic Los1 (or los1D) results in activation of the general amino acid control pathway (Qiu et al 2000;Karkusiewicz et al 2012) and, in the case of DNA damage, results in damage-induced temporary G1 checkpoint arrest (Ghavidel et al 2007). Thus, Los1 not only functions in tRNA nuclear export and tRNA quality control, but it also connects tRNA subcellular trafficking to cell physiology.…”

Maf1, repressor of tRNA transcription, is involved in the control of gluconeogenetic genes in Saccharomyces cerevisiae

“…In S. cerevisiae, unlike in vertebrates, intron-containing tRNA precursors are exported from the nucleus and pre-tRNA splicing occurs in the cytoplasm at the outer mitochondrial membrane (Yoshihisa et al, 2003). Significantly, strains lacking Maf1 do accumulate intron-containing tRNA precursors due to saturation of pretRNA nuclear export machinery (Karkusiewicz et al, 2011).…”