SRN1, a yeast gene involved in RNA processing, is identical to HEX2/REG1, a negative regulator in glucose repression.

Abstract

The yeast RNAI gene encodes a cytosolic protein that affects pre-tRNA splicing, pre-rRNA processing, the production of mRNA, and the export of RNA from the nucleus to the cytosol. In an attempt to understand how the RNA1 protein affects such a diverse set of processes, we sought second-site suppressors of a mutation, rnal-1, of the RNA] locus. Mutations in a single complementation group were obtained. These lesions proved to be in the same gene, SRNI, identified previously in a search for second-site suppressors of mutations that affect the removal of intervening sequences from pre-mRNAs. The SRNI gene was mapped, cloned, and sequenced. DNA sequence analysis and the phenotype of disruption mutations showed that, surprisingly, SRNI is identical to HEX2IREGI, a gene that negatively regulates glucose-repressible genes. Interestingly, SRNI is not a negative regulator ofRNAI at the transcriptional, translational, or protein stability level. However, SRNI does regulate the level of two newly discovered antigens, p43 and p70, one of which is not glucose repressible. These studies for the first time link RNA processing and carbon catabolite repression.Primary transcription products are often trimmed and modified to yield mature species via a series of processing steps. These processing steps may include 5' and 3' nucleotide alterations and splicing of intervening sequences, as well as addition and modification of nucleotides. In Saccharomyces cerevisiae, genes encoding some of the products necessary for RNA processing have been identified. The primary effect of mutations in these genes is usually at a specific step in the production of a single class of RNA. For example, mutations of the LOS1, SEN1, SEN2, TPD1, PTA1, and STPJ genes result in defects in the removal of intervening sequences from pre-tRNAs (for reviews, see references 5 and 11), whereas mutations in TRMI, MOD5, TRM2, and ML41 affect single nucleotide modifications of tRNAs (for a review, see reference 11). Mutations of the PRP genes affect the removal of intervening sequences from pre-mRNAs, causing a depletion of ribosomal proteins which in turn affects the accumulation of mature rRNAs (for a review, see reference 42).In contrast to the mutations in the genes described above, the mnal-1 mutation of the RNAJ gene (10) pleiotropically affects the processing of all three major classes of RNAs at the nonpermissive temperature. Processing of tRNA in rnal-1 cells is defective at the step of removal of the intervening sequence (12, 18), and rRNA is affected at the step of processing the 35S primary pre-rRNA (12). The defect in the production of mRNA in mal-1 cells is not clearly defined, but one report described elongated 3' ends (39) and another report described alterations in poly(A) lengths (33). Cells with the mal-1 allele are apparently not defective in the removal of intervening sequences from pre-mRNA (34). The transport of RNA from the nucleus to the cytosol is also affected by the mal-I mutation (15, 37).Paradoxically, it has been found that the RNA1 pr...

The REG2 Gene of Saccharomyces cerevisiae Encodes a Type 1 Protein Phosphatase-Binding Protein That Functions with Reg1p and the Snf1 Protein Kinase to Regulate Growth

“…REG1 encodes a 1,014-amino-acid product reported to be a negative regulator of glucose-repressible genes (21,51). In addition to its role in glucose repression, REG1 was isolated as an extragenic suppressor of rna1 mutants which are defective in both RNA processing and transport of RNA from the nucleus to the cytoplasm (57,79). The predicted protein products of REG1 and REG2 are 29% identical and 48% similar.…”

“…Along with the proposed role of REG1 as a negative regulator of glucose-repressible genes, reg1 mutants have been demonstrated to suppress RNA processing defects and temperature-sensitive growth of rna1-1 and prp mutants (49,57,79). The RNA1 gene encodes a cytosolic protein (38) shown to affect pre-tRNA and pre-tRNA processing (37,47) as well as transport of RNA from the nucleus to the cytoplasm (2,44,65).…”

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

“…Glc7 is the catalytic subunit of the phosphatase complex, whereas Reg1 is the regulatory subunit that targets the phosphatase to Snf1 since it can bind to the catalytic domain of the protein kinase. In yeast cells, lacking a proper Glc7-Reg1 function, the Snf1 kinase complex is constitutively active resulting in loss of glucose repression (Niederacher and Entian 1991;Tung et al 1992;Carlson 1994, 1995;Huang et al 1996;Hong et al 2005). However, gluconeogenic genes remain repressed in a reg1D strain, while genes involved in the utilization of alternative carbon sources are derepressed (Schuller 2003).…”

Histone H3 Ser10 Phosphorylation-Independent Function of Snf1 and Reg1 Proteins Rescues a gcn5− Mutant in HIS3 Expression

“…Suppressors that display gene specificity, instead of global effects on chromatin structure, may shed light on the molecular basis for Gcn5-mediated transcriptional activation. In our first attempt to identify the bypass of Gcn5 requirement gene (BGR) suppressors, we isolated one such mutation mapped to the REG1 gene.REG1 (also called HEX2 and SRN1) was identified in several genetic screens of glucose repression and RNA processing (63,65,66,96). Reg1 protein associates physically and functionally with an essential and multifunctional protein phosphatase 1, Glc7 (23,61,94), whose substrate specificity is apparently determined by association with different partners, including Reg1 protein.…”