The rapidly evolving X-linked MIR-506 family fine-tunes spermatogenesis to enhance sperm competition
- Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, United States
- The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, United States
- Developmental Biology Program, Sloan Kettering Institute, United States
- Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, United States
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
Figures
Figure 1 with 2 supplements
Genomic location, sequence alignment, and evolution conservation of the X-linked MIR-506 family.
(A) Genomic location of the X-linked MIR-506 family miRNAs (black bars) and the two flanking coding genes, SLITRK2 (green blocks) and FMR1 (red blocks). The number of miRNAs within each cluster is …
Figure 1—figure supplement 1
Multiz Alignment and Conservation analyses of X-linked MIR-506 family across 100 species using the human genomes as references.
miRNAs are highlighted in blue.
Figure 1—figure supplement 2
Genomic and sequence similarity among members of the X-linked MIR-506 family.
(A) Genomic similarity using GENIES-based dot plot analyses within clades. (B) Upper panel, sequences alignment of precursor Mir891 among primates. Lower panel, sequences alignment of precursor Mir89…
Figure 2 with 3 supplements
Evolutionary history of the X-linked MIR-506 family.
(A) Sequences alignment of FmiRs from various species using human MER91C DNA transposon as the reference. The first line is the human MER91C DNA transposon, and below are the miRNAs of various …
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Figure 2—source data 1
The original gel images of the MER91C DNA transposon-derived miRNAs from humans expressed in HEK293T cells in Figure 2E.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig2-data1-v1.zip
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Figure 2—source data 2
The PDF contains Figure 2E and the original gel images labeled with the relevant bands.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig2-data2-v1.zip
Figure 2—figure supplement 1
A phylogram of the X-linked MIR-506 family.
SmiRs and FmiRs are shown in cyan and blue, respectively.
Figure 2—figure supplement 2
A phylogenetic tree of the MER91C DNA transposons and the X-linked MIR-506 family miRNAs.
The MER91C DNA transposons are labeled in purple.
Figure 2—figure supplement 3
X-linked MIR-506 family is derived from MER91C DNA transposon and expanded via LINE retrotransposons.
(A) RNA structure and sRNA-seq reads of the MER91C DNA transposon-derived miRNAs in humans, marmosets, horses, and dogs. The mature miRNAs are labeled in blue in the RNA structure. (B) A …
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Figure 2—figure supplement 3—source data 1
The original gel images of the MER91C DNA transposon-derived miRNAs from horses and dogs expressed in HEK293T cells in Figure 2—figure supplement 3B.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig2-figsupp3-data1-v1.zip
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Figure 2—figure supplement 3—source data 2
The PDF contains Figure 2—figure supplement 3B and the original gel images labeled with the relevant bands.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig2-figsupp3-data2-v1.zip
Figure 3 with 1 supplement
Expression profiles of X-linked MIR-506 family in mammalian testes and male germ cells.
(A) Heatmaps showing the MIR-506 family expression in the testis, pachytene spermatocytes, round spermatids, and sperm in mice. Biological triplicates of the testis samples (n = 3) and duplicates of …
Figure 3—figure supplement 1
sRNA-seq of multiple tissues from different species.
(A) sRNA-seq from MirGeneDB across multiple tissues in humans. n = 1 for each group. (B) sRNA-seq from MirGeneDB across multiple tissues in rhesus. n = 1 for each group. (C) sRNA-seq from MirGeneDB …
Figure 4 with 1 supplement
Ablation of X-linked MIR-506 family miRNAs compromised sperm competitiveness and reproductive fitness in male mice.
(A) Schematics showing the strategy used to generate six lines of KO mice lacking individual or combined miRNA clusters within the MIR-506 family using CRISPR-Cas9. (B, C) Litter size (B) and litter …
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Figure 4—source data 1
The original gel images of the genotyping results of the sequential mating experiments in Figure 4H.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig4-data1-v1.zip
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Figure 4—source data 2
The PDF contains Figure 4H and the original gel images labeled with the relevant bands.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig4-data2-v1.zip
Figure 4—figure supplement 1
Phenotypes of MIR-506 family KO mice.
(A) The purity of pachytene spermatocytes and round spermatids after STA-PUT cell sorting in C57BL/6J mice. Scale bar = 25 μm. (B) Testis weight of WT and dKO mice. n = 3 for each sample. (C) Sperm …
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Figure 4—figure supplement 1—source data 1
The original gel images of the T7EI assay on the WT and quinKO mice genomic DNA from tail snips in Figure 4—figure supplement 1F.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig4-figsupp1-data1-v1.zip
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Figure 4—figure supplement 1—source data 2
The PDF contains Figure 4—figure supplement 1F and the original gel images labeled with the relevant bands.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig4-figsupp1-data2-v1.zip
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Figure 4—figure supplement 1—source data 3
The original gel images of genotyping the E10 embryos from co-artificial insemination in Figure 4—figure supplement 1J.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig4-figsupp1-data3-v1.zip
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Figure 4—figure supplement 1—source data 4
The PDF contains Figure 4—figure supplement 1J and the original gel images labeled with the relevant bands.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig4-figsupp1-data4-v1.zip
Figure 5 with 1 supplement
Target genes and genetic compensation of the X-linked MIR-506 family miRNAs.
(A) Intersections of the differentially expressed targets (DETs) among different KO testes. (B) GO term enrichment analyses of the 431 DETs shared among the four different MIR-506 family KO testes. …
Figure 5—figure supplement 1
Dysregulated targets in the X-linked MIR-506 family KO testes.
(A) Differentially expressed genes (DEGs) between KO and WT testes, n = 3 for each sample. Predicted targets are indicated as the triangle, and the genes with |log2FC| ≥ 1 and false discovery rate …
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Figure 5—figure supplement 1—source data 1
The original Western blot of CRISP1 in WT and quinKO testis samples in Figure 5—figure supplement 1E.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig5-figsupp1-data1-v1.zip
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Figure 5—figure supplement 1—source data 2
The PDF contains Figure 5—figure supplement 1E and the original WB images labeled with the relevant bands.
- https://cdn.elifesciences.org/articles/90203/elife-90203-fig5-figsupp1-data2-v1.zip
Figure 6 with 1 supplement
Rapid evolution of the X-linked MIR-506 family miRNAs correlates with increased complexity of genetic networks that regulate spermatogenesis across mammalian species.
(A) Overlap between the dysregulated targets in mice and the predicted targets in humans and rats. (B) Comparison of the cumulative distribution between the MIR-506 family targeting sites and the …
Figure 6—figure supplement 1
Dysregulated targets are shared across humans, mice, and rats.
(A) Luciferase assay of CRISP1 3′UTR and MIR-506 family miRNAs from humans. Three biological replicates were done for each sample. Left panel, the predicted binding sites for the MIR-506 family …
Author response image 1
sRNA-seq of WT and MIR-506 family KO testis samples.
Additional files
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Supplementary file 1
The X-linked MIR-506 family miRNAs in different species.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp1-v1.xlsx
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Supplementary file 2
TEs analysis for the X-linked MIR-506 family miRNAs.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp2-v1.xlsx
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Supplementary file 3
sRNA-seq analysis among different species.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp3-v1.xlsx
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Supplementary file 4
Male infertility associated with the X-linked MIR-506 family miRNAs in humans.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp4-v1.xlsx
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Supplementary file 5
Dysregulated large RNAs in the X-linked MIR-506 family miRNAs KO mice.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp5-v1.xlsx
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Supplementary file 6
Dysregulated small RNAs in the X-linked MIR-506 family miRNAs KO mice.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp6-v1.xlsx
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Supplementary file 7
Common targets of the X-linked MIR-506 family miRNAs among humans, mice, and rats.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp7-v1.xlsx
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Supplementary file 8
Primers used in this study.
- https://cdn.elifesciences.org/articles/90203/elife-90203-supp8-v1.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/90203/elife-90203-mdarchecklist1-v1.docx
