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Title: The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides

Abstract

Here, RNA interference (RNAi) is a conserved mechanism of genome defence that can also have a role in the regulation of endogenous functions through endogenous small RNAs (esRNAs). In fungi, knowledge of the functions regulated by esRNAs has been hampered by lack of clear phenotypes in most mutants affected in the RNAi machinery. Mutants of Mucor circinelloides affected in RNAi genes show defects in physiological and developmental processes, thus making Mucor an outstanding fungal model for studying endogenous functions regulated by RNAi. Some classes of Mucor esRNAs map to exons (ex-siRNAs) and regulate expression of the genes from which they derive. To have a broad picture of genes regulated by the silencing machinery during vegetative growth, we have sequenced and compared the mRNA profiles of mutants in the main RNAi genes by using RNA-seq. In addition, we have achieved a more complete phenotypic characterization of silencing mutants Deletion of any main RNAi gene provoked a deep impact in mRNA accumulation at exponential and stationary growth. Genes showing increased mRNA levels, as expected for direct ex-siRNAs targets, but also genes with decreased expression were detected, suggesting that, most probably, the initial ex-siRNA targets regulate the expression of other genes, which canmore » be up- or down-regulated. Expression of 50% of the genes was dependent on more than one RNAi gene in agreement with the existence of several classes of ex-siRNAs produced by different combinations of RNAi proteins. These combinations of proteins have also been involved in the regulation of different cellular processes. Besides genes regulated by the canonical RNAi pathway, this analysis identified processes, such as growth at low pH and sexual interaction that are regulated by a dicer-independent non-canonical RNAi pathway. In conclusion, this work shows that the RNAi pathways play a relevant role in the regulation of a significant number of endogenous genes in M. circinelloides during exponential and stationary growth phases and opens up an important avenue for in-depth study of genes involved in the regulation of physiological and developmental processes in this fungal model.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [1];  [1]
  1. Univ. of Murcia, Murcia (Spain)
  2. The Genome Analysis Centre, Norwich (United Kingdom)
Publication Date:
Research Org.:
USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1345508
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
BMC Genomics
Additional Journal Information:
Journal Volume: 16; Journal Issue: 1; Journal ID: ISSN 1471-2164
Publisher:
Springer
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; asexual sporulation; sexual interaction; pH regulation; non-canonical RNAi pathway; esRNAs; mRNA profiling

Citation Formats

Nicolas, Francisco E., Vila, Ana, Moxon, Simon, Cascales, Maria D., Torres-Martinez, Santiago, Ruiz-Vazquez, Rosa M., and Garre, Victoriano. The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides. United States: N. p., 2015. Web. doi:10.1186/s12864-015-1443-2.
Nicolas, Francisco E., Vila, Ana, Moxon, Simon, Cascales, Maria D., Torres-Martinez, Santiago, Ruiz-Vazquez, Rosa M., & Garre, Victoriano. The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides. United States. https://doi.org/10.1186/s12864-015-1443-2
Nicolas, Francisco E., Vila, Ana, Moxon, Simon, Cascales, Maria D., Torres-Martinez, Santiago, Ruiz-Vazquez, Rosa M., and Garre, Victoriano. Wed . "The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides". United States. https://doi.org/10.1186/s12864-015-1443-2. https://www.osti.gov/servlets/purl/1345508.
@article{osti_1345508,
title = {The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides},
author = {Nicolas, Francisco E. and Vila, Ana and Moxon, Simon and Cascales, Maria D. and Torres-Martinez, Santiago and Ruiz-Vazquez, Rosa M. and Garre, Victoriano},
abstractNote = {Here, RNA interference (RNAi) is a conserved mechanism of genome defence that can also have a role in the regulation of endogenous functions through endogenous small RNAs (esRNAs). In fungi, knowledge of the functions regulated by esRNAs has been hampered by lack of clear phenotypes in most mutants affected in the RNAi machinery. Mutants of Mucor circinelloides affected in RNAi genes show defects in physiological and developmental processes, thus making Mucor an outstanding fungal model for studying endogenous functions regulated by RNAi. Some classes of Mucor esRNAs map to exons (ex-siRNAs) and regulate expression of the genes from which they derive. To have a broad picture of genes regulated by the silencing machinery during vegetative growth, we have sequenced and compared the mRNA profiles of mutants in the main RNAi genes by using RNA-seq. In addition, we have achieved a more complete phenotypic characterization of silencing mutants Deletion of any main RNAi gene provoked a deep impact in mRNA accumulation at exponential and stationary growth. Genes showing increased mRNA levels, as expected for direct ex-siRNAs targets, but also genes with decreased expression were detected, suggesting that, most probably, the initial ex-siRNA targets regulate the expression of other genes, which can be up- or down-regulated. Expression of 50% of the genes was dependent on more than one RNAi gene in agreement with the existence of several classes of ex-siRNAs produced by different combinations of RNAi proteins. These combinations of proteins have also been involved in the regulation of different cellular processes. Besides genes regulated by the canonical RNAi pathway, this analysis identified processes, such as growth at low pH and sexual interaction that are regulated by a dicer-independent non-canonical RNAi pathway. In conclusion, this work shows that the RNAi pathways play a relevant role in the regulation of a significant number of endogenous genes in M. circinelloides during exponential and stationary growth phases and opens up an important avenue for in-depth study of genes involved in the regulation of physiological and developmental processes in this fungal model.},
doi = {10.1186/s12864-015-1443-2},
journal = {BMC Genomics},
number = 1,
volume = 16,
place = {United States},
year = {Wed Mar 25 00:00:00 EDT 2015},
month = {Wed Mar 25 00:00:00 EDT 2015}
}

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Works referenced in this record:

The RNAi Machinery in Mucorales: The Emerging Role of Endogenous Small RNAs
book, January 2014


Differentiation-Dependent Expression of 17β-Hydroxysteroid Dehydrogenase, Type 10, in the Rodent Testis: Effect of Aging in Leydig Cells
journal, July 2003

  • Ivell, Richard; Balvers, Marga; Anand, Ravinder J. K.
  • Endocrinology, Vol. 144, Issue 7
  • DOI: 10.1210/en.2002-0082

Calcineurin Plays Key Roles in the Dimorphic Transition and Virulence of the Human Pathogenic Zygomycete Mucor circinelloides
journal, September 2013


Photobiology in the Zygomycota: Multiple photoreceptor genes for complex responses to light
journal, November 2010


Two classes of small antisense RNAs in fungal RNA silencing triggered by non-integrative transgenes
journal, August 2003


Functional Analyses of Trichoderma reesei LAE1 Reveal Conserved and Contrasting Roles of This Regulator
journal, February 2013

  • Karimi-Aghcheh, Razieh; Bok, Jin Woo; Phatale, Pallavi A.
  • G3: Genes|Genomes|Genetics, Vol. 3, Issue 2
  • DOI: 10.1534/g3.112.005140

Effects of laeA deletion on Aspergillus flavus conidial development and hydrophobicity may contribute to loss of aflatoxin production
journal, February 2012


One Juliet and four Romeos: VeA and its methyltransferases
journal, January 2015

  • Sarikaya-Bayram, Özlem; Palmer, Jonathan M.; Keller, Nancy
  • Frontiers in Microbiology, Vol. 6
  • DOI: 10.3389/fmicb.2015.00001

The RNAi machinery regulates growth and development in the filamentous fungus Trichoderma atroviride: Function of sRNAs in Trichoderma
journal, June 2013

  • Carreras-Villaseñor, Nohemi; Esquivel-Naranjo, Edgardo U.; Villalobos-Escobedo, J. Manuel
  • Molecular Microbiology, Vol. 89, Issue 1
  • DOI: 10.1111/mmi.12261

Transcriptomic analysis of female and male gonads in juvenile snakeskin gourami (Trichopodus pectoralis)
journal, March 2020

  • Boonanuntanasarn, Surintorn; Jangprai, Araya; Na-Nakorn, Uthairat
  • Scientific Reports, Vol. 10, Issue 1
  • DOI: 10.1038/s41598-020-61738-0

Differential expression analysis for sequence count data
journal, October 2010


RNA Interference Pathways in Fungi: Mechanisms and Functions
journal, October 2012


Genetic control of asexual sporulation in filamentous fungi
journal, December 2012


Cell Integrity Signaling and Response to Stress in Fission Yeast
journal, December 2010


Small GTP-binding proteins are associated with chitosomes and vesicles carrying glucose oxidase from Mucor circinelloides
journal, March 2008

  • Moreno-Jiménez, Rocío; García-Soto, Jesús; Martínez-Cadena, Guadalupe
  • Microbiology, Vol. 154, Issue 3
  • DOI: 10.1099/mic.0.2007/012179-0

Necrotizing Cutaneous Mucormycosis after a Tornado in Joplin, Missouri, in 2011
journal, December 2012

  • Neblett Fanfair, Robyn; Benedict, Kaitlin; Bos, John
  • New England Journal of Medicine, Vol. 367, Issue 23
  • DOI: 10.1056/NEJMoa1204781

Origins and Mechanisms of miRNAs and siRNAs
journal, February 2009


Antifungal drug resistance evoked via RNAi-dependent epimutations
text, January 2014

  • J., Bastidas, Robert; E., Nicolás, Francisco; Chan, Lee, Soo
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/sh94-mh40

Small silencing RNAs: an expanding universe
journal, February 2009

  • Ghildiyal, Megha; Zamore, Phillip D.
  • Nature Reviews Genetics, Vol. 10, Issue 2
  • DOI: 10.1038/nrg2504

Zygomycosis: the re-emerging fungal infection
journal, March 2006

  • Chayakulkeeree, M.; Ghannoum, M. A.; Perfect, J. R.
  • European Journal of Clinical Microbiology & Infectious Diseases, Vol. 25, Issue 4
  • DOI: 10.1007/s10096-006-0107-1

Sporangiospore Size Dimorphism Is Linked to Virulence of Mucor circinelloides
journal, June 2011


Antifungal drug resistance evoked via RNAi-dependent epimutations
journal, July 2014

  • Calo, Silvia; Shertz-Wall, Cecelia; Lee, Soo Chan
  • Nature, Vol. 513, Issue 7519
  • DOI: 10.1038/nature13575

Protein O-mannosylation is crucial for cell wall integrity, septation and viability in fission yeast: S. pombe PMT family
journal, June 2005


Endogenous short RNAs generated by Dicer 2 and RNA-dependent RNA polymerase 1 regulate mRNAs in the basal fungus Mucor circinelloides
journal, April 2010

  • Nicolas, Francisco Esteban; Moxon, Simon; de Haro, Juan P.
  • Nucleic Acids Research, Vol. 38, Issue 16
  • DOI: 10.1093/nar/gkq301

Differential expression analysis for sequence count data
journal, April 2010


The Putative Protein Methyltransferase LAE1 of Trichoderma atroviride Is a Key Regulator of Asexual Development and Mycoparasitism
journal, June 2013


RNAi: a defensive RNA-silencing against viruses and transposable elements
journal, December 2005


Functional Diversity of RNAi-Associated sRNAs in Fungi
journal, July 2013

  • Nicolás, Francisco; Ruiz-Vázquez, Rosa
  • International Journal of Molecular Sciences, Vol. 14, Issue 8
  • DOI: 10.3390/ijms140815348

Epidemiology and Outcome of Zygomycosis: A Review of 929 Reported Cases
journal, September 2005

  • Roden, M. M.; Zaoutis, T. E.; Buchanan, W. L.
  • Clinical Infectious Diseases, Vol. 41, Issue 5
  • DOI: 10.1086/432579

Regulation of Autolysis in Aspergillus nidulans
journal, March 2008

  • Emri, Tamás; Molnár, Zsolt; Szilágyi, Melinda
  • Applied Biochemistry and Biotechnology, Vol. 151, Issue 2-3
  • DOI: 10.1007/s12010-008-8174-7

Mutants defective in a Mucor circinelloides dicer-like gene are not compromised in siRNA silencing but display developmental defects
journal, June 2007

  • Nicolás, Francisco E.; de Haro, Juan P.; Torres-Martínez, Santiago
  • Fungal Genetics and Biology, Vol. 44, Issue 6
  • DOI: 10.1016/j.fgb.2006.09.003

Increasing Incidence of Zygomycosis (Mucormycosis), France, 1997–2006
journal, September 2009

  • Bitar, Dounia; Van Cauteren, Dieter; Lanternier, Fanny
  • Emerging Infectious Diseases, Vol. 15, Issue 9
  • DOI: 10.3201/eid1509.090334

RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
journal, August 2011


A Single dicer Gene Is Required for Efficient Gene Silencing Associated with Two Classes of Small Antisense RNAs in Mucor circinelloides
journal, August 2009

  • de Haro, Juan P.; Calo, Silvia; Cervantes, María
  • Eukaryotic Cell, Vol. 8, Issue 10
  • DOI: 10.1128/EC.00191-09

Diverse Pathways Generate MicroRNA-like RNAs and Dicer-Independent Small Interfering RNAs in Fungi
journal, June 2010


Nutrition, Growth, and Morphogenesis of Mucor Rouxii
journal, January 1962


High-frequency heterokaryon formation by Mucor racemosus.
journal, January 1980


Enrichment method for the isolation of auxotrophic mutants of Mucor using the polyene antibiotic N-glycosyl-polifungin
journal, January 1984

  • Roncero, M. Isabel G.
  • Carlsberg Research Communications, Vol. 49, Issue 7
  • DOI: 10.1007/bf02907499

Zygomycosis: the re-emerging fungal infection
journal, March 2006

  • Chayakulkeeree, M.; Ghannoum, M. A.; Perfect, J. R.
  • European Journal of Clinical Microbiology & Infectious Diseases, Vol. 25, Issue 4
  • DOI: 10.1007/s10096-006-0107-1

Regulation of Autolysis in Aspergillus nidulans
journal, March 2008

  • Emri, Tamás; Molnár, Zsolt; Szilágyi, Melinda
  • Applied Biochemistry and Biotechnology, Vol. 151, Issue 2-3
  • DOI: 10.1007/s12010-008-8174-7

Origins and Mechanisms of miRNAs and siRNAs
journal, February 2009


Photobiology in the Zygomycota: Multiple photoreceptor genes for complex responses to light
journal, November 2010


Effects of laeA deletion on Aspergillus flavus conidial development and hydrophobicity may contribute to loss of aflatoxin production
journal, February 2012


Genetic control of asexual sporulation in filamentous fungi
journal, December 2012


Diverse Pathways Generate MicroRNA-like RNAs and Dicer-Independent Small Interfering RNAs in Fungi
journal, June 2010


Antifungal drug resistance evoked via RNAi-dependent epimutations
journal, July 2014

  • Calo, Silvia; Shertz-Wall, Cecelia; Lee, Soo Chan
  • Nature, Vol. 513, Issue 7519
  • DOI: 10.1038/nature13575

Small silencing RNAs: an expanding universe
journal, February 2009

  • Ghildiyal, Megha; Zamore, Phillip D.
  • Nature Reviews Genetics, Vol. 10, Issue 2
  • DOI: 10.1038/nrg2504

Opposing T cell responses in experimental autoimmune encephalomyelitis
journal, August 2019


Salinity tolerance mechanisms of an Arctic Pelagophyte using comparative transcriptomic and gene expression analysis
journal, May 2022


RNAi: a defensive RNA-silencing against viruses and transposable elements
journal, December 2005


Mucormycosis after a Tornado in Joplin, Missouri
journal, March 2013

  • Weddle, Gina M.; Pahud, B.; Jackson, M.
  • New England Journal of Medicine, Vol. 368, Issue 11, p. 1066-1067
  • DOI: 10.1056/nejmc1300111

Epidemiology and Outcome of Zygomycosis: A Review of 929 Reported Cases
journal, September 2005

  • Roden, M. M.; Zaoutis, T. E.; Buchanan, W. L.
  • Clinical Infectious Diseases, Vol. 41, Issue 5
  • DOI: 10.1086/432579

Two classes of small antisense RNAs in fungal RNA silencing triggered by non-integrative transgenes
journal, August 2003


Endogenous short RNAs generated by Dicer 2 and RNA-dependent RNA polymerase 1 regulate mRNAs in the basal fungus Mucor circinelloides
journal, April 2010

  • Nicolas, Francisco Esteban; Moxon, Simon; de Haro, Juan P.
  • Nucleic Acids Research, Vol. 38, Issue 16
  • DOI: 10.1093/nar/gkq301

Small GTP-binding proteins are associated with chitosomes and vesicles carrying glucose oxidase from Mucor circinelloides
journal, March 2008

  • Moreno-Jiménez, Rocío; García-Soto, Jesús; Martínez-Cadena, Guadalupe
  • Microbiology, Vol. 154, Issue 3
  • DOI: 10.1099/mic.0.2007/012179-0

Protein O-mannosylation is crucial for cell wall integrity, septation and viability in fission yeast: S. pombe PMT family
journal, June 2005


The RNAi machinery regulates growth and development in the filamentous fungus Trichoderma atroviride: Function of sRNAs in Trichoderma
journal, June 2013

  • Carreras-Villaseñor, Nohemi; Esquivel-Naranjo, Edgardo U.; Villalobos-Escobedo, J. Manuel
  • Molecular Microbiology, Vol. 89, Issue 1
  • DOI: 10.1111/mmi.12261

LaeA, a Regulator of Morphogenetic Fungal Virulence Factors
journal, September 2005


Fission Yeast Rho5p GTPase Is a Functional Paralogue of Rho1p That Plays a Role in Survival of Spores and Stationary-Phase Cells
journal, March 2006


High-frequency heterokaryon formation by Mucor racemosus.
journal, January 1980


Nutrition, Growth, and Morphogenesis of Mucor Rouxii
journal, January 1962


RNA Interference Pathways in Fungi: Mechanisms and Functions
journal, October 2012


Differentiation-Dependent Expression of 17β-Hydroxysteroid Dehydrogenase, Type 10, in the Rodent Testis: Effect of Aging in Leydig Cells
journal, July 2003

  • Ivell, Richard; Balvers, Marga; Anand, Ravinder J. K.
  • Endocrinology, Vol. 144, Issue 7
  • DOI: 10.1210/en.2002-0082

The Putative Protein Methyltransferase LAE1 of Trichoderma atroviride Is a Key Regulator of Asexual Development and Mycoparasitism
journal, June 2013


Calcineurin Plays Key Roles in the Dimorphic Transition and Virulence of the Human Pathogenic Zygomycete Mucor circinelloides
journal, September 2013


Functional Analyses of Trichoderma reesei LAE1 Reveal Conserved and Contrasting Roles of This Regulator
journal, February 2013

  • Karimi-Aghcheh, Razieh; Bok, Jin Woo; Phatale, Pallavi A.
  • G3: Genes|Genomes|Genetics, Vol. 3, Issue 2
  • DOI: 10.1534/g3.112.005140

Functional Diversity of RNAi-Associated sRNAs in Fungi
journal, July 2013

  • Nicolás, Francisco; Ruiz-Vázquez, Rosa
  • International Journal of Molecular Sciences, Vol. 14, Issue 8
  • DOI: 10.3390/ijms140815348

Works referencing / citing this record:

Mucor circinelloides : Growth, Maintenance, and Genetic Manipulation
journal, April 2018

  • Vellanki, Sandeep; Navarro-Mendoza, Maria Isabel; Garcia, Alexis
  • Current Protocols in Microbiology, Vol. 49, Issue 1
  • DOI: 10.1002/cpmc.53

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis
journal, January 2017

  • Trieu, Trung Anh; Navarro-Mendoza, María Isabel; Pérez-Arques, Carlos
  • PLOS Pathogens, Vol. 13, Issue 1
  • DOI: 10.1371/journal.ppat.1006150

A Non-canonical RNA Silencing Pathway Promotes mRNA Degradation in Basal Fungi
journal, April 2015


The interaction of fungi with the environment orchestrated by RNAi
journal, May 2016

  • Villalobos-Escobedo, José Manuel; Herrera-Estrella, Alfredo; Carreras-Villaseñor, Nohemí
  • Mycologia, Vol. 108, Issue 3
  • DOI: 10.3852/15-246

An Adult Zebrafish Model Reveals that Mucormycosis Induces Apoptosis of Infected Macrophages
journal, August 2018

  • López-Muñoz, Azucena; Nicolás, Francisco E.; García-Moreno, Diana
  • Scientific Reports, Vol. 8, Issue 1
  • DOI: 10.1038/s41598-018-30754-6

A non-canonical RNAi pathway controls virulence and genome stability in Mucorales
journal, July 2020


An Adult Zebrafish Model Reveals that Mucormycosis Induces Apoptosis of Infected Macrophages
journal, August 2018

  • López-Muñoz, Azucena; Nicolás, Francisco E.; García-Moreno, Diana
  • Scientific Reports, Vol. 8, Issue 1
  • DOI: 10.1038/s41598-018-30754-6

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis
journal, January 2017

  • Trieu, Trung Anh; Navarro-Mendoza, María Isabel; Pérez-Arques, Carlos
  • PLOS Pathogens, Vol. 13, Issue 1
  • DOI: 10.1371/journal.ppat.1006150