PMID- 36711716
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240325
DP  - 2024 Jan 9
TI  - The catalytic activity of microRNA Argonautes plays a modest role in microRNA 
      star strand destabilization in C. elegans.
LID - 2023.01.19.524782 [pii]
LID - 10.1101/2023.01.19.524782 [doi]
AB  - Many Argonaute proteins can cleave RNA ("slicing") as part of the 
      microRNA-induced silencing complex (miRISC), even though miRNA-mediated target 
      repression is generally independent of target cleavage. Here we use genome 
      editing in C. elegans to examine the role of miRNA-guided slicing in organismal 
      development. In contrast to previous work, slicing-inactivating mutations did not 
      interfere with normal development when introduced by CRISPR. We find that 
      unwinding and decay of miRNA star strands is weakly defective in the absence of 
      slicing, with the largest effect observed in embryos. Argonaute-Like Gene 2 
      (ALG-2) is more dependent on slicing for unwinding than ALG-1. The miRNAs that 
      displayed the greatest (albeit minor) dependence on slicing for unwinding tend to 
      form stable duplexes with their star strand, and in some cases, lowering duplex 
      stability alleviates dependence on slicing. Gene expression changes were 
      consistent with negligible to moderate loss of function for miRNA guides whose 
      star strand was upregulated, suggesting a reduced proportion of mature miRISC in 
      slicing mutants. While a few miRNA guide strands are reduced in the mutant 
      background, the basis of this is unclear since changes were not dependent on 
      EBAX-1, a factor in the Target-Directed miRNA Degradation (TDMD) pathway. 
      Overall, this work defines a role for miRNA Argonaute slicing in star strand 
      decay; future work should examine whether this role could have contributed to the 
      selection pressure to conserve catalytic activity of miRNA Argonautes across the 
      metazoan phylogeny.
FAU - Kotagama, Kasuen
AU  - Kotagama K
AD  - Laboratory of Cellular and Developmental Biology, NIDDK Intramural Research 
      Program, 50 South Drive, Bethesda, MD 20892, USA.
FAU - Grimme, Acadia L
AU  - Grimme AL
AD  - Laboratory of Cellular and Developmental Biology, NIDDK Intramural Research 
      Program, 50 South Drive, Bethesda, MD 20892, USA.
AD  - Johns Hopkins University Department of Biology, 3400 N. Charles Street, 
      Baltimore, MD 21218, USA.
FAU - Braviner, Leah
AU  - Braviner L
AD  - Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, 
      USA.
FAU - Yang, Bing
AU  - Yang B
AD  - Laboratory of Cellular and Developmental Biology, NIDDK Intramural Research 
      Program, 50 South Drive, Bethesda, MD 20892, USA.
FAU - Sakhawala, Rima M
AU  - Sakhawala RM
AD  - Laboratory of Cellular and Developmental Biology, NIDDK Intramural Research 
      Program, 50 South Drive, Bethesda, MD 20892, USA.
AD  - Johns Hopkins University Department of Biology, 3400 N. Charles Street, 
      Baltimore, MD 21218, USA.
FAU - Yu, Guoyun
AU  - Yu G
AD  - Laboratory of Cellular and Developmental Biology, NIDDK Intramural Research 
      Program, 50 South Drive, Bethesda, MD 20892, USA.
FAU - Benner, Lars Kristian
AU  - Benner LK
AD  - Laboratory of Cellular and Developmental Biology, NIDDK Intramural Research 
      Program, 50 South Drive, Bethesda, MD 20892, USA.
AD  - Current address: Johns Hopkins University Department of Biology, 3400 N. Charles 
      Street, Baltimore, MD 21218, USA.
FAU - Joshua-Tor, Leemor
AU  - Joshua-Tor L
AD  - Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, 
      USA.
FAU - McJunkin, Katherine
AU  - McJunkin K
AUID- ORCID: 0000-0001-9730-442X
AD  - Laboratory of Cellular and Developmental Biology, NIDDK Intramural Research 
      Program, 50 South Drive, Bethesda, MD 20892, USA.
LA  - eng
GR  - P40 OD010440/OD/NIH HHS/United States
PT  - Preprint
DEP - 20240109
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - Nucleic Acids Res. 2024 Mar 12;:. PMID: 38471816
PMC - PMC9882359
EDAT- 2023/01/31 06:00
MHDA- 2023/01/31 06:01
PMCR- 2024/01/12
CRDT- 2023/01/30 03:55
PHST- 2023/01/31 06:00 [pubmed]
PHST- 2023/01/31 06:01 [medline]
PHST- 2023/01/30 03:55 [entrez]
PHST- 2024/01/12 00:00 [pmc-release]
AID - 2023.01.19.524782 [pii]
AID - 10.1101/2023.01.19.524782 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Jan 9:2023.01.19.524782. doi: 10.1101/2023.01.19.524782.