PMID- 33877360
OWN - NLM
STAT- MEDLINE
DCOM- 20210706
LR  - 20231111
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 49
IP  - 9
DP  - 2021 May 21
TI  - A ribonuclease III involved in virulence of Mucorales fungi has evolved to cut 
      exclusively single-stranded RNA.
PG  - 5294-5307
LID - 10.1093/nar/gkab238 [doi]
AB  - Members of the ribonuclease III (RNase III) family regulate gene expression by 
      processing double-stranded RNA (dsRNA). This family includes eukaryotic Dicer and 
      Drosha enzymes that generate small dsRNAs in the RNA interference (RNAi) pathway. 
      The fungus Mucor lusitanicus, which causes the deadly infection mucormycosis, has 
      a complex RNAi system encompassing a non-canonical RNAi pathway (NCRIP) that 
      regulates virulence by degrading specific mRNAs. In this pathway, Dicer function 
      is replaced by R3B2, an atypical class I RNase III, and small single-stranded 
      RNAs (ssRNAs) are produced instead of small dsRNA as Dicer-dependent RNAi 
      pathways. Here, we show that R3B2 forms a homodimer that binds to ssRNA and dsRNA 
      molecules, but exclusively cuts ssRNA, in contrast to all known RNase III. The 
      dsRNA cleavage inability stems from its unusual RNase III domain (RIIID) because 
      its replacement by a canonical RIIID allows dsRNA processing. A crystal structure 
      of R3B2 RIIID resembles canonical RIIIDs, despite the low sequence conservation. 
      However, the groove that accommodates dsRNA in canonical RNases III is narrower 
      in the R3B2 homodimer, suggesting that this feature could be responsible for the 
      cleavage specificity for ssRNA. Conservation of this activity in R3B2 proteins 
      from other mucormycosis-causing Mucorales fungi indicates an early evolutionary 
      acquisition.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Canovas-Marquez, Jose Tomas
AU  - Canovas-Marquez JT
AUID- ORCID: 0000-0001-6608-4145
AD  - Department of Genetics and Microbiology (Associated Unit to IQFR-CSIC), Faculty 
      of Biology, University of Murcia, 30100 Murcia, Spain.
FAU - Falk, Sebastian
AU  - Falk S
AUID- ORCID: 0000-0001-7848-4621
AD  - Department of Structural and Computational Biology, Max Perutz Labs, A-1030 
      Vienna, Austria.
FAU - Nicolas, Francisco E
AU  - Nicolas FE
AUID- ORCID: 0000-0003-3762-5971
AD  - Department of Genetics and Microbiology (Associated Unit to IQFR-CSIC), Faculty 
      of Biology, University of Murcia, 30100 Murcia, Spain.
FAU - Padmanabhan, Subramanian
AU  - Padmanabhan S
AUID- ORCID: 0000-0002-8772-0152
AD  - Instituto de Quimica Fisica "Rocasolano," Consejo Superior de Investigaciones 
      Cientificas, 28006 Madrid, Spain.
FAU - Zapata-Perez, Ruben
AU  - Zapata-Perez R
AUID- ORCID: 0000-0003-4432-9652
AD  - Department of Biochemistry and Molecular Biology-A, Faculty of Biology, Regional 
      Campus of International Excellence "Campus Mare Nostrum," University of Murcia, 
      Campus Espinardo, 30100, Murcia, Spain.
FAU - Sanchez-Ferrer, Alvaro
AU  - Sanchez-Ferrer A
AUID- ORCID: 0000-0001-7266-4402
AD  - Department of Biochemistry and Molecular Biology-A, Faculty of Biology, Regional 
      Campus of International Excellence "Campus Mare Nostrum," University of Murcia, 
      Campus Espinardo, 30100, Murcia, Spain.
FAU - Navarro, Eusebio
AU  - Navarro E
AUID- ORCID: 0000-0002-3091-4378
AD  - Department of Genetics and Microbiology (Associated Unit to IQFR-CSIC), Faculty 
      of Biology, University of Murcia, 30100 Murcia, Spain.
FAU - Garre, Victoriano
AU  - Garre V
AUID- ORCID: 0000-0001-7605-1726
AD  - Department of Genetics and Microbiology (Associated Unit to IQFR-CSIC), Faculty 
      of Biology, University of Murcia, 30100 Murcia, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Fungal Proteins)
RN  - 63231-63-0 (RNA)
RN  - EC 3.1.26.3 (Ribonuclease III)
SB  - IM
MH  - Evolution, Molecular
MH  - Fungal Proteins/*chemistry/genetics/*metabolism
MH  - Models, Molecular
MH  - Mucor/*enzymology
MH  - Mucorales/enzymology/pathogenicity
MH  - Protein Domains
MH  - RNA/metabolism
MH  - Ribonuclease III/*chemistry/genetics/*metabolism
MH  - Virulence
PMC - PMC8136814
EDAT- 2021/04/21 06:00
MHDA- 2021/07/07 06:00
PMCR- 2021/04/20
CRDT- 2021/04/20 12:20
PHST- 2021/03/24 00:00 [accepted]
PHST- 2021/02/16 00:00 [revised]
PHST- 2020/07/22 00:00 [received]
PHST- 2021/04/21 06:00 [pubmed]
PHST- 2021/07/07 06:00 [medline]
PHST- 2021/04/20 12:20 [entrez]
PHST- 2021/04/20 00:00 [pmc-release]
AID - 6240633 [pii]
AID - gkab238 [pii]
AID - 10.1093/nar/gkab238 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2021 May 21;49(9):5294-5307. doi: 10.1093/nar/gkab238.