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...

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Main Authors: Jason Gabunilas, Guillaume Chanfreau
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-04-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC4838235?pdf=render
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author Jason Gabunilas
Guillaume Chanfreau
author_facet Jason Gabunilas
Guillaume Chanfreau
author_sort Jason Gabunilas
collection DOAJ
description 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.
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spelling doaj.art-d066d5f080bd4df48203f49687277a742022-12-22T02:59:58ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-04-01124e100599910.1371/journal.pgen.1005999Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.Jason GabunilasGuillaume ChanfreauIn 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.http://europepmc.org/articles/PMC4838235?pdf=render
spellingShingle Jason Gabunilas
Guillaume Chanfreau
Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.
PLoS Genetics
title Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.
title_full Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.
title_fullStr Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.
title_full_unstemmed Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.
title_short Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.
title_sort splicing mediated autoregulation modulates rpl22p expression in saccharomyces cerevisiae
url http://europepmc.org/articles/PMC4838235?pdf=render
work_keys_str_mv AT jasongabunilas splicingmediatedautoregulationmodulatesrpl22pexpressioninsaccharomycescerevisiae
AT guillaumechanfreau splicingmediatedautoregulationmodulatesrpl22pexpressioninsaccharomycescerevisiae