Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, splicing is critical for expression of ribosomal protein genes (RPGs), which are among the most highly expressed genes and are tightly regulated according to growth and environmental conditions. However, knowledge of the precise mechanisms by which RPG pre-mRNA splicing is regulated on a gene-by-gene basis is lacking. Here we show that Rpl22p has an extraribosomal role in the inhibition of splicing of the RPL22B pre-mRNA transcript. A stem loop secondary structure within the intron is necessary for pre-mRNA binding by Rpl22p in vivo and splicing inhibition in vivo and in vitro and can rescue splicing inhibition in vitro when added in trans to splicing reactions. Splicing inhibition by Rpl22p may be partly attributed to the reduction of co-transcriptional U1 snRNP recruitment to the pre-mRNA at the RPL22B locus. We further demonstrate that the inhibition of RPL22B pre-mRNA splicing contributes to the down-regulation of mature transcript during specific stress conditions, and provide evidence hinting at a regulatory role for this mechanism in conditions of suppressed ribosome biogenesis. These results demonstrate an autoregulatory mechanism that fine-tunes the expression of the Rpl22 protein and by extension Rpl22p paralog composition according to the cellular demands for ribosome biogenesis.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, United States of America.
Jason
J
Gabunilas
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, United States of America.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
Guillaume
http://orcid.org/0000-0002-2505-1950
G
Chanfreau
D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing / Q000502:physiology*; D012331:RNA, Fungal / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D012269:Ribosomal Proteins / Q000096:biosynthesis* / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D012322:RNA Precursors; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D012269:Ribosomal Proteins; C000609793:Rpl22 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins