. Author manuscript; available in PMC: 2022 Sep 16.

Published in final edited form as: Nat Rev Genet. 2020 Feb 12;21(5):311–331. doi: 10.1038/s41576-019-0203-6

Table 1 |.

The functions and phenotypes of RNAi in eukaryotes

Organism	Chromosomal functions and phenotypes	Genome integrity functions and phenotypes
S. pombe	*dcr1Δ, ago1Δ, and rdp1Δ - Lagging chromosomes and missegregation in dividing cells, quiescence entry, and meiosis (small RNA)^71–75 dcr1*Δ - reduction in rDNA copy number¹⁸¹	*dcr1Δ and ago1Δ - sensitive to HU (indicative of replication stress-induced damage), accumulate DNA damage (Rad22 foci), and are synthetic lethal with rad51A^180,195,196 dcr1*Δ - damage at repetitive loci and highly expressed genes, loses rDNA copy number^180,181
N. crassa	SAD-1 (Rdrp), DCL-1, SMS-2 (Ago) – required for MSUD post-transcriptional dosage control (small RNA)^147–150 DCL-1/2, QDE-2 (Ago), and QDE-1 (Rdrp) – loss of this pathway reduces copy number at repetitive loci such as the rDNA (small RNA)¹⁸⁵	DCL-1/2, QDE-2 (Ago), and QDE-1 (Rdrp) – generate damage induced siRNAs (qiRNAs) that interact with repair machinery, (small RNA)¹⁸⁴
T. thermophila	Dcl1 knockout - lagging/bridging during mitosis and meiosis⁶⁶ Dcl1, Twi1P (Ago/Piwi) drive the DNA elimination pathway (small rna)^66,165,172
T. brucei	TbAgo1 knockout – chromosome missegregation, whole genome aneuploidy (small RNA)⁸⁸
H. sapiens	**DICER1 or AGO2** knockdown – lagging chromosomes in RPE-1, HeLa cells^93,102	DICER1/DROSHA – knockdown increases DNA damage in fibroblasts (γH2A.X)¹⁹⁰ DICER1/DROSHA/AGO2 – production of DNA damage-induced small RNAs and direction of chromatin/repair machinery to DSB (small RNA)^{199,206,207,209,210} DICER1/DGCR8 – assist in nucleotide excision repair possibly at the chromatin level^214–216
M. musculus	*Dicer1* knockout – lagging chromosomes in fibroblasts⁹⁷	DICER1/DROSHA – knockdown increases DNA damage (γH2A.X) in NIH2/4 cells, cerebellum, and mESCs^193,190 DICER1/DROSHA/AGO2 – production of DNA damage-induced small RNAs and direction of repair machinery to DSB in NIH2/4 cells (small RNA)²⁰⁵
D. melanogaster	Dcr-2 and Ago2 deletion/knockdown – lagging chromosomes in wing disc, S2 cells, and embryos (small RNA)^93,94 Dcr-2 – mutant has reduced H3K9me2 at rDNA and an increase in rDNA circles¹⁸⁸ Dcr-2 and Ago2 loss of function mutations – synthetic lethal with roX1/roX2 doubles, indicating role in X chromosome recognition for dosage compensation through 1.688^X satellite repeat siRNAs (small RNA)^161,162	Dcr2 knockout – increase in DNA damage (γH2A.X)¹⁸⁹ Dcr-2 and Ago2 – generate damage-induced small RNAs (small RNA)²⁰¹
C. elegans	CSR-1 (Ago) knockdown – chromosome segregation defects in embryo and meiosis (small RNA)^65,129 DCR-1 knockout – misshapen oocytes with high DNA content, X chromosome missegregation in male meiosis^130,131,138 CSR-1 mutants have reduced H3K9me2 on unpaired X chromosome and increased H3K9me2 on autosomes in early meiosis¹³⁵	DCR-1 – loss of function mutant shows disruption of nucleotide excision repair upon UV treatment²¹⁴
A. thaliana	AGO4 knockout – lagging/bridging chromosomes reported during mitosis and male meiosis (small RNA)⁹⁵ easiRNAs (dependent on microRNA to trigger formation) sense whole genome dosage in interploidy hybrids (small RNA)^32,144,145	DCLs and AGO2 - generation of damage induced siRNAs (diRNAs) (small RNA)¹⁹⁹ RDR2, DCL-4, and AGO1 – production of uviRNAs in GG-NER UV damage response (small aRNA)²¹⁷
Z. mays	AGO104 loss of function mutation – disruption of chromosome condensation and segregation during male meiosis, also shows the formation of micronuclei and multinucleated cells (small RNA)¹⁴²