Puf4 regulates both splicing and decay of HXL1 mRNA encoding the unfolded protein response transcription factor in Cryptococcus neoformans.

Eukaryotic Cell Pub Date : 2015-04-01 Epub Date: 2015-02-13 DOI:10.1128/EC.00273-14
Virginia E Glazier, Jan Naseer Kaur, Nancy T Brown, Ashley A Rivera, John C Panepinto
{"title":"Puf4 regulates both splicing and decay of HXL1 mRNA encoding the unfolded protein response transcription factor in Cryptococcus neoformans.","authors":"Virginia E Glazier,&nbsp;Jan Naseer Kaur,&nbsp;Nancy T Brown,&nbsp;Ashley A Rivera,&nbsp;John C Panepinto","doi":"10.1128/EC.00273-14","DOIUrl":null,"url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) responds to errors in protein folding or processing by induction of the unfolded protein response (UPR). During conditions of ER stress, unconventional splicing of an mRNA encoding the UPR-responsive transcription factor occurs at the ER surface, resulting in activation of the UPR. UPR activation is necessary for adaptation to ER stress and for the pathogenic fungus Cryptococcus neoformans is an absolute requirement for temperature adaptation and virulence. In this study, we have determined that C. neoformans has co-opted a conserved PUF RNA binding protein to regulate the posttranscriptional processing of the HXL1 mRNA encoding the UPR transcription factor. PUF elements were identified in both the 5' and 3' untranslated regions of the HXL1 transcript, and both elements bound Puf4. Deletion of PUF4 resulted in delayed unconventional splicing of HXL1 mRNA and delayed induction of Hxl1 target genes. In addition, the HXL1 transcript was stabilized in the absence of Puf4. The puf4Δ mutant exhibited temperature sensitivity but was as virulent as the wild type, despite a reduction in fungal burden in the brains of infected mice. Our results reveal a novel regulatory role in which a PUF protein influences the unconventional splicing of the mRNA encoding the UPR-responsive transcription factor. These data suggest a unique role for a PUF protein in controlling UPR kinetics via the posttranscriptional regulation of the mRNA encoding the UPR transcription factor Hxl1. </p>","PeriodicalId":11891,"journal":{"name":"Eukaryotic Cell","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/EC.00273-14","citationCount":"17","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Eukaryotic Cell","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1128/EC.00273-14","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2015/2/13 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 17

Abstract

The endoplasmic reticulum (ER) responds to errors in protein folding or processing by induction of the unfolded protein response (UPR). During conditions of ER stress, unconventional splicing of an mRNA encoding the UPR-responsive transcription factor occurs at the ER surface, resulting in activation of the UPR. UPR activation is necessary for adaptation to ER stress and for the pathogenic fungus Cryptococcus neoformans is an absolute requirement for temperature adaptation and virulence. In this study, we have determined that C. neoformans has co-opted a conserved PUF RNA binding protein to regulate the posttranscriptional processing of the HXL1 mRNA encoding the UPR transcription factor. PUF elements were identified in both the 5' and 3' untranslated regions of the HXL1 transcript, and both elements bound Puf4. Deletion of PUF4 resulted in delayed unconventional splicing of HXL1 mRNA and delayed induction of Hxl1 target genes. In addition, the HXL1 transcript was stabilized in the absence of Puf4. The puf4Δ mutant exhibited temperature sensitivity but was as virulent as the wild type, despite a reduction in fungal burden in the brains of infected mice. Our results reveal a novel regulatory role in which a PUF protein influences the unconventional splicing of the mRNA encoding the UPR-responsive transcription factor. These data suggest a unique role for a PUF protein in controlling UPR kinetics via the posttranscriptional regulation of the mRNA encoding the UPR transcription factor Hxl1.

Abstract Image

Abstract Image

Abstract Image

在新型隐球菌中,Puf4调节编码未折叠蛋白应答转录因子的HXL1 mRNA的剪接和衰减。
内质网(ER)通过诱导未折叠蛋白反应(UPR)来响应蛋白质折叠或加工中的错误。在内质网应激条件下,编码UPR应答转录因子的mRNA在内质网表面发生非常规剪接,导致UPR激活。UPR激活是适应内质网胁迫的必要条件,对于致病性新隐球菌来说,UPR激活是温度适应和毒力的绝对要求。在这项研究中,我们已经确定C. neoformmans已经选择了一个保守的PUF RNA结合蛋白来调节编码UPR转录因子的HXL1 mRNA的转录后加工。在HXL1转录本的5′和3′非翻译区均发现PUF元件,这两个元件均结合Puf4。PUF4的缺失导致HXL1 mRNA的非常规剪接延迟,HXL1靶基因的诱导延迟。此外,在没有Puf4的情况下,HXL1转录物是稳定的。puf4Δ突变体表现出温度敏感性,但毒性与野生型一样,尽管感染小鼠大脑中的真菌负荷减少。我们的研究结果揭示了一种新的调控作用,其中PUF蛋白影响编码uprr应答转录因子的mRNA的非常规剪接。这些数据表明,PUF蛋白通过编码UPR转录因子Hxl1的mRNA的转录后调控,在控制UPR动力学中发挥了独特的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Eukaryotic Cell
Eukaryotic Cell 生物-微生物学
自引率
0.00%
发文量
0
审稿时长
1 months
期刊介绍: Eukaryotic Cell (EC) focuses on eukaryotic microbiology and presents reports of basic research on simple eukaryotic microorganisms, such as yeasts, fungi, algae, protozoa, and social amoebae. The journal also covers viruses of these organisms and their organelles and their interactions with other living systems, where the focus is on the eukaryotic cell. Topics include: - Basic biology - Molecular and cellular biology - Mechanisms, and control, of developmental pathways - Structure and form inherent in basic biological processes - Cellular architecture - Metabolic physiology - Comparative genomics, biochemistry, and evolution - Population dynamics - Ecology
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信